The f_LT Response Function of D(e,e'p)n at Q^2=0.33(GeV/c)^2

The interference response function f_LT (R_LT) of the D(e,e'p)n reaction has been determined at squared four-momentum transfer Q^2 = 0.33 (GeV/c)^2 and for missing momenta up to p_miss= 0.29 (GeV/c). The results have been compared to calculations that reproduce f_LT quite well but overestimate the cross sections by 10 - 20% for missing momenta between 0.1 (GeV/c) and 0.2 (GeV/c) .Comment: 12 Pages, 10 figure

A measurement of the axial form factor of the nucleon by the p(e,e'pi+)n reaction at W=1125 MeV

The reaction p(e,e'pi+)n was measured at the Mainz Microtron MAMI at an invariant mass of W=1125 MeV and four-momentum transfers of Q^2=0.117, 0.195 and 0.273 (GeV/c)^2. For each value of Q^2, a Rosenbluth separation of the transverse and longitudinal cross sections was performed. An effective Lagrangian model was used to extract the `axial mass' from experimental data. We find a value of M_A=(1.077+-0.039) GeV which is (0.051+-0.044) GeV larger than the axial mass known from neutrino scattering experiments. This is consistent with recent calculations in chiral perturbation theory.Comment: 14 pages, 5 figures, uses elsart.cl

Measurement of the recoil polarization in the p (\vec e, e' \vec p) pi^0 reaction at the \Delta(1232) resonance

The recoil proton polarization has been measured in the p (\vec e,e'\vec p) pi^0 reaction in parallel kinematics around W = 1232 MeV, Q^2 = 0.121 (GeV/c)^2 and epsilon = 0.718 using the polarized c.w. electron beam of the Mainz Microtron. Due to the spin precession in a magnetic spectrometer, all three proton polarization components P_x/P_e = (-11.4 \pm 1.3 \pm 1.4) %, P_y = (-43.1 \pm 1.3 \pm 2.2) %, and P_z/P_e = (56.2 \pm 1.5 \pm 2.6) % could be measured simultaneously. The Coulomb quadrupole to magnetic dipole ratio CMR = (-6.4\pm 0.7_{stat}\pm 0.8_{syst}) % was determined from P_x in the framework of the Mainz Unitary Isobar Model. The consistency among the reduced polarizations and the extraction of the ratio of longitudinal to transverse response is discussed.Comment: 5 pages LaTeX, 1 table, 2 eps figure

The first determination of Generalized Polarizabilities of the proton by a Virtual Compton Scattering experiment

Absolute differential cross sections for the reaction (e+p -> e+p+gamma) have been measured at a four-momentum transfer with virtuality Q^2=0.33 GeV^2 and polarization \epsilon = 0.62 in the range 33.6 to 111.5 MeV/c for the momentum of the outgoing photon in the photon-proton center of mass frame. The experiment has been performed with the high resolution spectrometers at the Mainz Microtron MAMI. From the photon angular distributions, two structure functions which are a linear combination of the generalized polarizabilities have been determined for the first time.Comment: 4 pages, 3 figure

UHRF genes regulate programmed interdigital tissue regression and chondrogenesis in the embryonic limb

The primordium of the limb contains a number of progenitors far superior to those necessary to form the skeletal components of this appendage. During the course of development, precursors that do not follow the skeletogenic program are removed by cell senescence and apoptosis. The formation of the digits provides the most representative example of embryonic remodeling via cell degeneration. In the hand/foot regions of the embryonic vertebrate limb (autopod), the interdigital tissue and the zones of interphalangeal joint formation undergo massive degeneration that accounts for jointed and free digit morphology. Developmental senescence and caspase-dependent apoptosis are considered responsible for these remodeling processes. Our study uncovers a new upstream level of regulation of remodeling by the epigenetic regulators Uhrf1 and Uhrf2 genes. These genes are spatially and temporally expressed in the pre-apoptotic regions. UHRF1 and UHRF2 showed a nuclear localization associated with foci of methylated cytosine. Interestingly, nuclear labeling increased in cells progressing through the stages of degeneration prior to TUNEL positivity. Functional analysis in cultured limb skeletal progenitors via the overexpression of either UHRF1 or UHRF2 inhibited chondrogenesis and induced cell senescence and apoptosis accompanied with changes in global and regional DNA methylation. Uhrfs modulated canonical cell differentiation factors, such as Sox9 and Scleraxis, promoted apoptosis via up-regulation of Bak1, and induced cell senescence, by arresting progenitors at the S phase and upregulating the expression of p21. Expression of Uhrf genes in vivo was positively modulated by FGF signaling. In the micromass culture assay Uhrf1 was down-regulated as the progenitors lost stemness and differentiated into cartilage. Together, our findings emphasize the importance of tuning the balance between cell differentiation and cell stemness as a central step in the initiation of the so-called ?embryonic programmed cell death? and suggest that the structural organization of the chromatin, via epigenetic modifications, may be a precocious and critical factor in these regulatory events.Funding: We thank Montse Fernandez Calderon, Susana Dawalibi, and Sonia Perez Mantecon, for excellent technical assistance. This work was supported by a Grant (BFU2017-84046-P) from the Spanish Science and Innovation Ministry to J.A.M

Measurement of the beam-helicity asymmetry in the p(e_pol,e'p)pi_0 reaction at the energy of the Delta(1232) resonance

In a p(e_pol,e'p)pi_0 out-of-plane coincidence experiment at the 3-spectrometer setup of the Mainz Microtron MAMI, the beam-helicity asymmetry has been precisely measured around the energy of the Delta(1232) resonance and Q^2 = 0.2 (GeV/c)^2. The results are in disagreement with three up-to-date model calculations. This is interpreted as lack of understanding of the non-resonant background, which in dynamical models is related to the pion cloud.Comment: 5 pages, 2 figures, 2 table

Experimental Verification of a Predicted Intronic MicroRNA in Human NGFR Gene with a Potential Pro-Apoptotic Function

Neurotrophins (NTs) are a family of secreted growth factor proteins primarily involved in the regulation of survival and appropriate development of neural cells, functioning by binding to their specific (TrkA, TtkB, and TrkC) and/or common NGFR receptor. NGFR is the common receptor of NTs, binding with low-affinity to all members of the family. Among different functions assigned to NGFR, it is also involved in apoptosis induction and tumorigenesis processes. Interestingly, some of the functions of NGFR appear to be ligand-independent, suggesting a probable involvement of non-coding RNA residing within the sequence of the gene. Here, we are reporting the existence of a conserved putative microRNA, named Hsa-mir-6165 [EBI accession#: FR873488]. Transfection of a DNA segment corresponding to the pre-mir-6165 sequence in Hela cell line caused the generation of mature exogenous mir-6165 (a ∼200,000 fold overexpression). Furthermore, using specific primers, we succeeded to detect the endogenous expression of mir-6165 in several glioma cell lines and glioma primary tumors known to express NGFR. Similar to the pro-apoptotic role of NGFR in some cell types, overexpression of pre-mir-6165 in U87 cell line resulted in an elevated rate of apoptosis. Moreover, coordinated with the increased level of mir-6165 in the transfected U87 cell line, two of its predicted target genes (Pkd1 and DAGLA) were significantly down-regulated. The latter findings suggest that some of the previously attributed functions of NGFR could be explained indirectly by co-transcription of mir-6165 in the cells

LNCaP Atlas: Gene expression associated with in vivo progression to castration-recurrent prostate cancer

<p>Abstract</p> <p>Background</p> <p>There is no cure for castration-recurrent prostate cancer (CRPC) and the mechanisms underlying this stage of the disease are unknown.</p> <p>Methods</p> <p>We analyzed the transcriptome of human LNCaP prostate cancer cells as they progress to CRPC <it>in vivo </it>using replicate LongSAGE libraries. We refer to these libraries as the LNCaP atlas and compared these gene expression profiles with current suggested models of CRPC.</p> <p>Results</p> <p>Three million tags were sequenced using <it>in vivo </it>samples at various stages of hormonal progression to reveal 96 novel genes differentially expressed in CRPC. Thirty-one genes encode proteins that are either secreted or are located at the plasma membrane, 21 genes changed levels of expression in response to androgen, and 8 genes have enriched expression in the prostate. Expression of 26, 6, 12, and 15 genes have previously been linked to prostate cancer, Gleason grade, progression, and metastasis, respectively. Expression profiles of genes in CRPC support a role for the transcriptional activity of the androgen receptor (<it>CCNH, CUEDC2, FLNA, PSMA7</it>), steroid synthesis and metabolism (<it>DHCR24, DHRS7</it>, <it>ELOVL5, HSD17B4</it>, <it>OPRK1</it>), neuroendocrine (<it>ENO2, MAOA, OPRK1, S100A10, TRPM8</it>), and proliferation (<it>GAS5</it>, <it>GNB2L1</it>, <it>MT-ND3</it>, <it>NKX3-1</it>, <it>PCGEM1</it>, <it>PTGFR</it>, <it>STEAP1</it>, <it>TMEM30A</it>), but neither supported nor discounted a role for cell survival genes.</p> <p>Conclusions</p> <p>The <it>in vivo </it>gene expression atlas for LNCaP was sequenced and support a role for the androgen receptor in CRPC.</p

Anchors aweigh: the sources, variety, and challenges of mission drift

The growing number of studies which reference the concept of mission drift imply that such drift is an undesirable strategic outcome related to inconsistent organizational action, yet beyond such references little is known about how mission drift occurs, how it impacts organizations, and how organizations should respond. Existing management theory more broadly offers initial albeit equivocal insight for understanding mission drift. On the one hand, prior studies have argued that inconsistent or divergent action can lead to weakened stakeholder commitment and reputational damage. On the other hand, scholars have suggested that because environments are complex and dynamic, such action is necessary for ensuring organizational adaptation and thus survival. In this study, we offer a theory of mission drift that unpacks its origin, clarifies its variety, and specifies how organizations might respond to external perceptions of mission drift. The resulting conceptual model addresses the aforementioned theoretical tension and offers novel insight into the relationship between organizational actions and identity