Recombinant Vgr-1/BMP-6-expressing tumors induce fibrosis and endochondral bone formation in vivo.

Members of the TGF-beta superfamily appear to modulate mesenchymal differentiation, including the processes of cartilage and bone formation. Nothing is yet known about the function of the TGF-beta-related factor vgr-1, also called bone morphogenetic protein-6 (BMP-6), and only limited studies have been conducted on the most closely related factors BMP-5, osteogenic protein-1 (OP-1) or BMP-7, and OP-2. Because vgr-1 mRNA has been localized in hypertrophic cartilage, this factor may play a vital role in endochondral bone formation. We developed antibodies to vgr-1, and documented that vgr-1 protein was expressed in hypertrophic cartilage of mice. To further characterize the role of this protein in bone differentiation, we generated CHO cells that overexpressed recombinant murine vgr-1 protein. Western blot analysis documented that recombinant vgr-1 protein was secreted into the media and was proteolytically processed to yield the mature vgr-1 molecule. To assess the biological activity of recombinant vgr-1 in vivo, we introduced the vgr-1-expressing CHO cells directly into the subcutaneous tissue of athymic nude mice. CHO-vgr-1 cells produced localized tumors, and the continuous secretion of vgr-1 resulted in tumors with a strikingly different gross and histological appearance as compared to the parental CHO cells. The tumors of control CHO cells were hemorrhagic, necrotic, and friable, whereas the CHO-vgr-1 tumors were dense, firm, and fibrotic. In contrast with control CHO tumors, the nests of CHO-vgr-1 tumor cells were surrounded by extensive connective tissue, which contained large regions of cartilage and bone. Further analysis indicated that secretion of vgr-1 from the transfected CHO tumor cells induced the surrounding host mesenchymal cells to develop along the endochondral bone pathway. These findings suggest that endochondral bone formation

Chemical potential oscillations from a single nodal pocket in the underdoped high-Tc superconductor YBa2Cu3O6+x

The mystery of the normal state in the underdoped cuprates has deepened with the use of newer and complementary experimental probes. While photoemission studies have revealed solely `Fermi arcs' centered on nodal points in the Brillouin zone at which holes aggregate upon doping, more recent quantum oscillation experiments have been interpreted in terms of an ambipolar Fermi surface, that includes sections containing electron carriers located at the antinodal region. To address the question of whether an ambipolar Fermi surface truly exists, here we utilize measurements of the second harmonic quantum oscillations, which reveal that the amplitude of these oscillations arises mainly from oscillations in the chemical potential, providing crucial information on the nature of the Fermi surface in underdoped YBa2Cu3O6+x. In particular, the detailed relationship between the second harmonic amplitude and the fundamental amplitude of the quantum oscillations leads us to the conclusion that there exists only a single underlying quasi-two dimensional Fermi surface pocket giving rise to the multiple frequency components observed via the effects of warping, bilayer splitting and magnetic breakdown. A range of studies suggest that the pocket is most likely associated with states near the nodal region of the Brillouin zone of underdoped YBa2Cu3O6+x at high magnetic fields.Comment: 7 pages, 4 figure

A Spectral Line Survey from 138.3 to 150.7 GHZ toward Orion-KL

We present the results of a spectral line survey from 138.3 to 150.7 GHz toward Orion-KL. The observations were made using the 14 m radio telescope of Taeduk Radio Astronomy Observatory. Typical system temperatures were between 500 and 700 K, with the sensitivity between $0.02 - 0.06$ K in units of $\rm T_A^*$. A total of 149 line spectra are detected in this survey. Fifty lines have been previously reported, however we find 99 new detections. Among these new lines, 32 are `unidentified', while 67 are from molecular transitions with known identifications. There is no detection of H or He recombination lines. The identified spectra are from a total of 16 molecular species and their isotopic variants. In the range from 138.3 to 150.7 GHz, the strongest spectral line is the J=3-2 transition of CS molecule, followed by transitions of the $\rm H_2CO$, $\rm CH_3OH$, $\rm CH_3CN$, and $\rm SO_2$. Spectral lines from the large organic molecules such as $\rm CH_3OH$, $\rm CH_3OCH_3$, $\rm HCOOCH_3$, $\rm C_2H_5CN$ and $\rm CH_3CN$ are prominent; with 80 % of the identified lines arising from transitions of these molecules. The rotational temperatures and column densities are derived using the standard rotation diagram analysis for $\rm CH_3OH$ ($\rm ^{13}CH_3OH$), $\rm HCOOCH_3$, $\rm CH_3CN$ and $\rm SO_2$ with $\rm 10\sim 270 K$ and $\rm 0.2\sim 20\times 10^{15} cm^{-2}$. These estimates are fairly comparable to the values for the same molecule in other frequency regions by other studies.Comment: 10 figures, 2 tex files for a manuscript and tables, accepted to Ap

Quantum linear amplifier enhanced by photon subtraction and addition

A deterministic quantum amplifier inevitably adds noise to an amplified signal due to the uncertainty principle in quantum physics. We here investigate how a quantum-noise-limited amplifier can be improved by additionally employing the photon subtraction, the photon addition, and a coherent superposition of the two, thereby making a probabilistic, heralded, quantum amplifier. We show that these operations can enhance the performance in amplifying a coherent state in terms of intensity gain, fidelity, and phase uncertainty. In particular, the photon subtraction turns out to be optimal for the fidelity and the phase concentration among these elementary operations, while the photon addition also provides a significant reduction in the phase uncertainty with the largest gain effect.Comment: published version, 7 pages, 9 figure

Peer review and citation data in predicting university rankings, a large-scale analysis

Most Performance-based Research Funding Systems (PRFS) draw on peer review and bibliometric indicators, two different method- ologies which are sometimes combined. A common argument against the use of indicators in such research evaluation exercises is their low corre- lation at the article level with peer review judgments. In this study, we analyse 191,000 papers from 154 higher education institutes which were peer reviewed in a national research evaluation exercise. We combine these data with 6.95 million citations to the original papers. We show that when citation-based indicators are applied at the institutional or departmental level, rather than at the level of individual papers, surpris- ingly large correlations with peer review judgments can be observed, up to r <= 0.802, n = 37, p < 0.001 for some disciplines. In our evaluation of ranking prediction performance based on citation data, we show we can reduce the mean rank prediction error by 25% compared to previous work. This suggests that citation-based indicators are sufficiently aligned with peer review results at the institutional level to be used to lessen the overall burden of peer review on national evaluation exercises leading to considerable cost savings

Vertical beaming of wavelength-scale photonic crystal resonators

We report that $> 80$ of the photons generated inside a photonic crystal slab resonator can be funneled within a small divergence angle of $\pm 30^\circ$. The far-field radiation properties of a photonic crystal slab resonant mode are modified by tuning the cavity geometry and by placing a reflector below the cavity. The former method directly shapes the near-field distribution so as to achieve directional and linearly-polarized far-field patterns. The latter modification takes advantage of the interference effect between the original waves and the reflected waves to enhance the energy-directionality. We find that, regardless of the slab thickness, the optimum distance between the slab and the reflector closely equals one wavelength of the resonance under consideration. We have also discussed an efficient far-field simulation algorithm based on the finite-difference time-domain method and the near- to far-field transformation.Comment: 14 pages, 15 figures, submitted to Phys. Rev.

Mechanical activation of vinculin binding to talin locks talin in an unfolded conformation

The force-dependent interaction between talin and vinculin plays a crucial role in the initiation and growth of focal adhesions. Here we use magnetic tweezers to characterise the mechano-sensitive compact N-terminal region of the talin rod, and show that the three helical bundles R1-R3 in this region unfold in three distinct steps consistent with the domains unfolding independently. Mechanical stretching of talin R1-R3 enhances its binding to vinculin and vinculin binding inhibits talin refolding after force is released. Mutations that stabilize R3 identify it as the initial mechano-sensing domain in talin, unfolding at ~5 pN, suggesting that 5 pN is the force threshold for vinculin binding and adhesion progression

A dynamic network approach for the study of human phenotypes

The use of networks to integrate different genetic, proteomic, and metabolic datasets has been proposed as a viable path toward elucidating the origins of specific diseases. Here we introduce a new phenotypic database summarizing correlations obtained from the disease history of more than 30 million patients in a Phenotypic Disease Network (PDN). We present evidence that the structure of the PDN is relevant to the understanding of illness progression by showing that (1) patients develop diseases close in the network to those they already have; (2) the progression of disease along the links of the network is different for patients of different genders and ethnicities; (3) patients diagnosed with diseases which are more highly connected in the PDN tend to die sooner than those affected by less connected diseases; and (4) diseases that tend to be preceded by others in the PDN tend to be more connected than diseases that precede other illnesses, and are associated with higher degrees of mortality. Our findings show that disease progression can be represented and studied using network methods, offering the potential to enhance our understanding of the origin and evolution of human diseases. The dataset introduced here, released concurrently with this publication, represents the largest relational phenotypic resource publicly available to the research community.Comment: 28 pages (double space), 6 figure

Quantization of Integrable Systems and a 2d/4d Duality

We present a new duality between the F-terms of supersymmetric field theories defined in two- and four-dimensions respectively. The duality relates N=2 supersymmetric gauge theories in four dimensions, deformed by an Omega-background in one plane, to N=(2,2) gauged linear sigma-models in two dimensions. On the four dimensional side, our main example is N=2 SQCD with gauge group SU(L) and 2L fundamental flavours. Using ideas of Nekrasov and Shatashvili, we argue that the Coulomb branch of this theory provides a quantization of the classical Heisenberg SL(2) spin chain. Agreement with the standard quantization via the Algebraic Bethe Ansatz implies the existence of an isomorphism between the chiral ring of the 4d theory and that of a certain two-dimensional theory. The latter can be understood as the worldvolume theory on a surface operator/vortex string probing the Higgs branch of the same 4d theory. We check the proposed duality by explicit calculation at low orders in the instanton expansion. One striking consequence is that the Seiberg-Witten solution of the 4d theory is captured by a one-loop computation in two dimensions. The duality also has interesting connections with the AGT conjecture, matrix models and topological string theory where it corresponds to a refined version of the geometric transition.Comment: 51 pages, 7 figures. Additional comments, minor improvements and references adde