Androgen receptor functions in prostate cancer development and progression

The androgen receptor (AR) is critical for the normal development of prostate and for its differentiated functions. The consistent expression of AR in prostate cancer (PCa), and its continued activity in PCa that relapse after androgen deprivation therapy (castration-resistant prostate cancer (CRPC)), indicate that at least a subset of these genes are also critical for PCa development and progression. This review addressed AR regulated genes that may be critical for PCa, and how AR may acquire new functions during PCa development and progression

Quantized Landau level spectrum and its density dependence

Scanning tunneling microscopy and spectroscopy in magnetic field was used to study Landau quantization in graphene and its dependence on charge carrier density. Measurements were carried out on exfoliated graphene samples deposited on a chlorinated SiO2 thermal oxide which allowed observing the Landau level sequences characteristic of single layer graphene while tuning the density through the Si backgate. Upon changing the carrier density we find abrupt jumps in the Fermi level after each Landau level is filled. Moreover, the Landau level spacing shows a marked increase at low doping levels, consistent with an interaction-induced renormalization of the Dirac cone.Comment: 11 pages, 4 figure

Choice of vasopressor in septic shock: does it matter?

Septic shock is a medical emergency that is associated with mortality rates of 40–70%. Prompt recognition and institution of effective therapy is required for optimal outcome. When the shock state persists after adequate fluid resuscitation, vasopressor therapy is required to improve and maintain adequate tissue/organ perfusion in an attempt to improve survival and prevent the development of multiple organ dysfunction and failure. Controversy surrounding the optimum choice of vasopressor strategy to utilize in the management of patients with septic shock continues. A recent randomized study of epinephrine compared to norepinephrine (plus dobutamine when indicated) leads to more questions than answers

AR, the cell cycle, and prostate cancer

The androgen receptor (AR) is a critical effector of prostate cancer development and progression. The dependence of this tumor type on AR activity is exploited in treatment of disseminated prostate cancers, wherein ablation of AR function (achieved either through ligand depletion and/or the use of AR antagonists) is the first line of therapeutic intervention. These strategies are initially effective, and induce a mixed response of cell cycle arrest or apoptosis in prostate cancer cells. However, recurrent, incurable tumors ultimately arise as a result of inappropriately restored AR function. Based on these observations, it is imperative to define the mechanisms by which AR controls cancer cell proliferation. Mechanistic investigation has revealed that AR acts as a master regulator of G1-S phase progression, able to induce signals that promote G1 cyclin-dependent kinase (CDK) activity, induce phosphorylation/inactivation of the retinoblastoma tumor suppressor (RB), and thereby govern androgen-dependent proliferation. These functions appear to be independent of the recently identified TMPRSS2-ETS fusions. Once engaged, several components of the cell cycle machinery actively modulate AR activity throughout the cell cycle, thus indicating that crosstalk between the AR and cell cycle pathways likely modulate the mitogenic response to androgen. As will be discussed, discrete aberrations in this process can alter the proliferative response to androgen, and potentially subvert hormonal control of tumor progression

Tau Polarization in Λb→Xcτνˉ \Lambda_b \to X_c \tau \bar{\nu} and B→XcτνˉB \to X_c \tau \bar{\nu}

We discuss the longitudinal and transverse $\tau$-polarization in inclusive decays of hadrons containing $b$-quarks. The calculation is performed by means of an OPE in HQET. Some mathematical difficulties in calculating transverse polarizations are explained. Numerical results are presented for longitudinal and for transverse polarizations, both in and perpendicular to the decay plane.Comment: LATEX, 20 pages, 5 Postscript figure

High Resolution Electron Beam Induced Current Measurements in an Scanning Tunneling Microscope on GaAs-MESFET

Recently, the first results of electron beam induced current (EBIC) measurements in a scanning tunneling microscope (STM) have been reported. Although the acquired results match with those obtained in conventional EBIC investigations, the interpretation of the obtained results is still restricted solely to a qualitative discussion. In this paper, a quantitative approach is used for two-dimensional numerical simulations of induced currents in GaAs-MESFET leading to a first starting point for a sophisticated interpretation of the dependence of induced currents on experimental and device parameters

Development of an Scanning Tunneling Microscopy-Based Electron Beam Induced Current (EBIC) Microscope

Measurements of electron beam induced currents (EBIC) can either be performed in a scanning electron microscope (SEM) or in a scanning tunneling microscope (STM), since both microscopes are very similar in their basic assembly. However, a straightforward application of an STM in EBIC-measurements, i.e. the use of a microscope tip as a fine source for low energetic electrons is not possible due to the specific demands on the instrument in an EBIC application. The present paper gives a compilation of these demands and describes their conversion into an optimized STM-EBIC microscope

Measurements of Nanoscale Domain Wall Flexing in a Ferromagnetic Thin Film

We use the high spatial sensitivity of the anomalous Hall effect in the ferromagnetic semiconductor Ga1-xMnxAs, combined with the magneto-optical Kerr effect, to probe the nanoscale elastic flexing behavior of a single magnetic domain wall in a ferromagnetic thin film. Our technique allows position sensitive characterization of the pinning site density, which we estimate to be around 10^14 cm^{-3}. Analysis of single site depinning events and their temperature dependence yields estimates of pinning site forces (10 pN range) as well as the thermal deactivation energy. Finally, our data hints at a much higher intrinsic domain wall mobility for flexing than previously observed in optically-probed micron scale measurements

Requirements for CD1d Recognition by Human Invariant Vα24+ CD4−CD8− T Cells

A subset of human CD4−CD8− T cells that expresses an invariant Vα24-JαQ T cell receptor (TCR)-α chain, paired predominantly with Vβ11, has been identified. A series of these Vα24 Vβ11 clones were shown to have TCR-β CDR3 diversity and express the natural killer (NK) locus–encoded C-type lectins NKR-P1A, CD94, and CD69. However, in contrast to NK cells, they did not express killer inhibitory receptors, CD16, CD56, or CD57. All invariant Vα24+ clones recognized the MHC class I–like CD16 molecule and discriminated between CD1d and other closely related human CD1 proteins, indicating that recognition was TCR-mediated. Recognition was not dependent upon an endosomal targeting motif in the cytoplasmic tail of CD1d. Upon activation by anti-CD3 or CD1d, the clones produced both Th1 and Th2 cytokines. These results demonstrate that human invariant Vα24+ CD4−CD8− T cells, and presumably the homologous murine NK1+ T cell population, are CD1d reactive and functionally distinct from NK cells. The conservation of this cell population and of the CD1d ligand across species indicates an important immunological function

Correlation Between Microstructure and Thermionic Electron Emission from Os-Ru Thin Films on Dispenser Cathodes

Osmium-ruthenium films with different microstructures were deposited onto dispenser cathodes and subjected to 1000 h of close-spaced diode testing. Tailored microstructures were achieved by applying substrate biasing during deposition, and these were evaluated with scanning electron microscopy, x-ray diffraction, and energy dispersive x-ray spectroscopy before and after close-spaced diode testing. Knee temperatures determined from the close-spaced diode test data were used to evaluate cathode performance. Cathodes with a large {10-11} Os-Ru film texture possessed comparatively low knee temperatures. Furthermore, a low knee temperature correlated with a low effective work function as calculated from the close-spaced diode data. It is proposed that the formation of strong {10-11} texture is responsible for the superior performance of the cathode with a multilayered Os-Ru coating