MicroRNA expression profiling assays have shown that miR-34b/c and miR-449a are down-regulated in nasopharyngeal carcinoma (NPC); however, the targets and functions of miR-34b/c and miR-449a in the pathologenesis of NPC remain elusive. In this study, we verified miR-34b/c and miR-449a were significantly reduced with the advance of NPC. Overexpression of miR-34b-3 and miR-449a suppressed the growth of NPC cells in culture and mouse tumor xenografts. Using tandem mass tags for quantitative labeling and LC-MS/MS analysis to investigate protein changes after restoring expression of miR-34b-3, 251 proteins were found to be down-regulated after miR-34b-3 transfection. Through 3 replicate experiments, we found that miR-34b-3 regulated the expression of 15 potential targeted genes mainly clustered in the key enzymes of glycolysis metabolism, including lactate dehydrogenase A (LDHA). Further investigation revealed that miR-34b-3 and miR-449a negatively regulated LDHA by binding to the 3′ untranslated regions of LDHA. Furthermore, LDHA overexpression rescued the miR-34b-3 and miR-449a induced tumor inhibition effect in CNE2 cells. In addition, miR-34b-3 and miR-449a suppressed LDH activity and reduced LD content, which were directly induced by downregulation of the LDHA. Our findings suggest that miR-34b-3 and miR-449a suppress the development of NPC through regulation of glycolysis via targeting LDHA and may be potential therapeutic targets for the treatment of NPC.

Growth of the axial and appendicular skeleton depends on endochondral ossification, which is controlled by tightly regulated cell–cell interactions in the developing growth plates. Previous studies have uncovered an important role of a disintegrin and metalloprotease 17 (ADAM17) in the normal development of the mineralized zone of hypertrophic chondrocytes during endochondral ossification. ADAM17 regulates EGF-receptor signaling by cleaving EGFR-ligands such as TGFα from their membrane-anchored precursor. The activity of ADAM17 is controlled by two regulatory binding partners, the inactive Rhomboids 1 and 2 (iRhom1, 2), raising questions about their role in endochondral ossification. To address this question, we generated mice lacking iRhom2 (iR2−/−) with floxed alleles of iRhom1 that were specifically deleted in chondrocytes by Col2a1-Cre (iR1∆Ch). The resulting iR2−/−iR1∆Ch mice had retarded bone growth compared to iR2−/− mice, caused by a significantly expanded zone of hypertrophic mineralizing chondrocytes in the growth plate. Primary iR2−/−iR1∆Ch chondrocytes had strongly reduced shedding of TGFα and other ADAM17-dependent EGFR-ligands. The enlarged zone of mineralized hypertrophic chondrocytes in iR2−/−iR1∆Ch mice closely resembled the abnormal growth plate in A17∆Ch mice and was similar to growth plates in Tgfα−/− mice or mice with EGFR mutations. These data support a model in which iRhom1 and 2 regulate bone growth by controlling the ADAM17/TGFα/EGFR signaling axis during endochondral ossification.

We present a protocol for an atomic interferometer that reaches the Heisenberg Limit (HL), within a factor of ∼ √ 2, via collective state detection and critical tuning of one-axis twist spin squeezing. It generates a Schrödinger cat (SC) state, as a superposition of two extremal collective states. When this SC interferometer is used as a gyroscope, the interference occurs at an ultrahigh Compton frequency, corresponding to a mesoscopic single object with a mass of N m, where N is the number of particles in the ensemble, and m is the mass of each particle. For 87 Rb atoms, with N = 10 6 , for example, the intereference would occur at a Compton frequency of ∼ 2 × 10 31 Hz. Under this scheme, the signal is found to depend critically on the parity of N . We present two variants of the protocol. Under Protocol A, the fringes are narrowed by a factor of N for one parity, while for the other parity the signal is zero. Under Protocol B, the fringes are narrowed by a factor of N for one parity, and by a factor of √ N for the other parity. Both protocols can be modified in a manner that reverses the behavior of the signals for the two parities. Over repeated measurements under which the probability of being even or odd is equal, the averaged sensitivity is smaller than the HL by a factor of ∼ √ 2 for both versions of the protocol. We describe an experimental scheme for realizing such an atomic interferometer, and discuss potential limitations due to experimental constraints imposed by the current state of the art, for both collective state detection and oneaxis-twist squeezing. We show that when the SC interferometer is configured as an accelerometer, the effective two-photon wave vector is enhanced by a factor of N , leading to the same degree of enhancement in sensitivity. We also show that such a mesoscopic single object can be used to increase the effective base frequency of an atomic clock by a factor of N , with a sensitivity that is equivalent to the HL, within a factor of ∼ √ 2.

We propose an arbitrary pattern lithography process using interference of Bose-Einstein Condensates (BEC). A symmetric three pulse Raman atom interferometer (AI) is used to implement the system. The pattern information, in the form of a phase-only mask, is optically encoded into the BEC order parameter in one of the AI arms. The lithographic pattern is represented by a two-dimensional intensity variation, and is transformed into a two-dimensional phase variation in the BEC order parameter via the use of AC-stark shift induced by a pulsed laser field. The BEC probability distribution of the interference result at the end of the AI is proportional to the required pattern. In order to produce features smaller than the diffraction limit for the used optical elements, we employ a three-dimensional atomic lens system to scale down the resulting pattern. The operating conditions for this lens structure are investigated in order to identify practical constraints. Simulations of the overall system using the parameters of 87 Rb BEC were performed to illustrate its functionality. The proposed process, while perhaps not suitable for general purpose usage, may enable the creation of special purpose patterns on a very small scale, with features as small as few nanometers.

We investigate the behavior of an ensemble of N non-interacting, identical atoms, excited by a laser. In general, the i-th atom sees a Rabi frequency Ω i , an initial position dependent laser phase φ i , and a motion induced Doppler shift of δ i . When Ω i or δ i is distinct for each atom, the system evolves into a superposition of 2 N intercoupled states, of which there are N + 1 symmetric and (2 N − (N + 1)) asymmetric collective states. For a collective state atomic interferometer (COSAIN) we recently proposed, it is important to understand the behavior of all the collective states under various conditions. In this paper, we show how to formulate the properties of these states under various non-idealities, and use this formulation to understand the dynamics thereof.We also consider the effect of treating the center of mass degree of freedom of the atoms quantum mechanically on the description of the collective states, illustrating that it is indeed possible to construct a generalized collective state, as needed for the COSAIN, when each atom is assumed to be in a localized wave packet. The analysis presented in this paper is important for understanding the dynamics of the COSAIN, and will help advance the analysis and optimization of spin squeezing in the presence of practically unavoidable non-idealities as well as in the domain where the center of mass motion of the atoms is quantized.

We describe a collective state atomic clock (COSAC) with Ramsey fringes narrowed by a factor of √ N compared to a conventional clock -N being the number of non-interacting atoms -without violating the uncertainty relation. This narrowing is explained as being due to interferences among the collective states, representing an effective √ N fold increase in the clock frequency, without entanglement. We discuss the experimental inhomogeneities that affect the signal and show that experimental parameters can be adjusted to produce a near ideal signal. The detection process collects fluorescence through stimulated Raman scattering of Stokes photons, which emits photons predominantly in the direction of the probe beam for a high enough optical density. By using a null measurement scheme, in which detection of zero photons corresponds to the system being in a single collective state, we detect the population in a collective state of interest. The quantum and classical noise of the ideal COSAC is still limited by the standard quantum limit and performs only as well as the conventional clock. However, when detection efficiency and collection efficiency are taken into account, the detection scheme of the COSAC increases the quantum efficiency of detection significantly in comparison to a typical conventional clock employing fluorescence detection, yielding a net improvement in stability by as much as a factor of 10.

In a conventional atomic interferometer employing N atoms, the phase sensitivity is at the standard quantum limit: 1/ √ N . Using spin-squeezing, the sensitivity can be increased, either by lowering the quantum noise or via phase amplification, or a combination thereof. Here, we show how to increase the sensitivity, to the Heisenberg limit of 1/N , while increasing the quantum noise by √ N , thereby suppressing by the same factor the effect of excess noise. The proposed protocol makes use of a Schrödinger Cat state representing a mesoscopic superposition of two collective states of N atoms, behaving as a single entity with an N -fold increase in Compton frequency. The resulting N -fold phase magnification is revealed by using atomic state detection instead of collective state detection. We also show how to realize an atomic clock based on such a Schrödinger Cat state, with an N -fold increase in the effective transition frequency. We also discuss potential experimental constraints for implementing this scheme, using one axis twist squeezing employing the cavity feedback scheme, and show that the effects of cavity decay and spontaneous emission are highly suppressed due to the N -fold phase magnification. We find that even for a modest value of the cavity cooperativity parameter that should be readily accessible experimentally, the maximum improvement in sensitivity is very close to the ideal limit, for as many as ten million atoms.PACS numbers: 06.30. Gv, 03.75.Dg, 37.25.+k Using the fact that Ȯ = tr(ρÔ) for any operatorÔ, it

In a conventional atomic interferometer employing N atoms, the phase sensitivity is at the standard quantum limit: 1 / N . Under usual spin squeezing, the sensitivity is increased by lowering the quantum noise. It is also possible to increase the sensitivity by leaving the quantum noise unchanged while producing phase amplification. Here we show how to increase the sensitivity, to the Heisenberg limit of 1 / N , while increasing the quantum noise by N and amplifying the phase by a factor of N . Because of the enhancement of the quantum noise and the large phase magnification, the effect of excess noise is highly suppressed. The protocol uses a Schrödinger cat state representing a maximally entangled superposition of two collective states of N atoms. The phase magnification occurs when we use either atomic state detection or collective state detection; however, the robustness against excess noise occurs only when atomic state detection is employed. We show that for one version of the protocol, the signal amplitude is N when N is even, and is vanishingly small when N is odd, for both types of detection. We also show how the protocol can be modified to reverse the nature of the signal for odd versus even values of N . Thus, for a situation where the probability of N being even or odd is equal, the net sensitivity is within a factor of 2 of the Heisenberg limit. Finally, we discuss potential experimental constraints for implementing this scheme via one-axis-twist squeezing employing the cavity feedback scheme, and show that the effects of cavity decay and spontaneous emission are highly suppressed because of the increased quantum noise and the large phase magnification inherent to the protocol. As a result, we find that the maximum improvement in sensitivity can be close to the ideal limit for as many as 10 million atoms.