Cancer Patient T Cells Genetically Targeted to Prostate-Specific Membrane Antigen Specifically Lyse Prostate Cancer Cells and Release Cytokines in Response to Prostate-Specific Membrane Antigen

AbstractThe expression of immunoglobulin-based artificial receptors in normal T lymphocytes provides a means to target lymphocytes to cell surface antigens independently of major histocompatibility complex restriction. Such artificial receptors have been previously shown to confer antigen-specific tumoricidal properties in murine T cells. We constructed a novel ζ chain fusion receptor specific for prostate-specific membrane antigen (PSMA) termed Pz-1. PSMA is a cell-surface glycoprotein expressed on prostate cancer cells and the neovascular endothelium of multiple carcinomas. We show that primary T cells harvested from five of five patients with different stages of prostate cancer and transduced with the Pz-1 receptor readily lyse prostate cancer cells. Having established a culture system using fibroblasts that express PSMA, we next show that T cells expressing the Pz-1 receptor release cytokines in response to cell-bound PSMA. Furthermore, we show that the cytokine release is greatly augmented by B7.1-mediated costimulation. Thus, our findings support the feasibility of adoptive cell therapy by using genetically engineered T cells in prostate cancer patients and suggest that both CD4+ and CD8+ T lymphocyte functions can be synergistically targeted against tumor cells

Comparison of K+K^+ and e−e^- Quasielastic Scattering

We formulate $K^+$-nucleus quasielastic scattering in a manner which closely parallels standard treatments of $e^-$-nucleus quasielastic scattering. For $K^+$ scattering, new responses involving scalar contributions appear in addition to the Coulomb (or longitudinal) and transverse $(e,e')$ responses which are of vector character. We compute these responses using both nuclear matter and finite nucleus versions of the Relativistic Hartree Approximation to Quantum Hadrodynamics including RPA correlations. Overall agreement with measured $(e,e')$ responses and new $K^+$ quasielastic scattering data for $^{40}$Ca at |\qs|=500 MeV/c is good. Strong RPA quenching is essential for agreement with the Coulomb response. This quenching is notably less for the $K^+$ cross section even though the new scalar contributions are even more strongly quenched than the vector contributions. We show that this ``differential quenching'' alters sensitive cancellations in the expression for the $K^+$ cross section so that it is reduced much less than the individual responses. We emphasize the role of the purely relativistic distinction between vector and scalar contributions in obtaining an accurate and consistent description of the $(e,e')$ and $K^+$ data within the framework of our nuclear structure model.Comment: 26 pages, 5 uuencoded figures appended to end of this fil

Positron Annihilation in the Galaxy

The 511 keV line from positron annihilation in the Galaxy was the first γ-ray line detected to originate from outside our solar system. Going into the fifth decade since the discovery, the source of positrons is still unconfirmed and remains one of the enduring mysteries in γ-ray astronomy. With a large flux of ∼10−3 γ/cm2/s, after 15 years in operation INTEGRAL/SPI has detected the 511 keV line at >50σ and has performed high-resolution spectral studies which conclude that Galactic positrons predominantly annihilate at low energies in warm phases of the interstellar medium. The results from imaging are less certain, but show a spatial distribution with a strong concentration in the center of the Galaxy. The observed emission from the Galactic disk has low surface brightness and the scale height is poorly constrained, therefore, the shear number of annihilating positrons in our Galaxy is still not well know. Positrons produced in β+-decay of nucleosynthesis products, such as 26Al, can account for some of the annihilation emission in the disk, but the observed spatial distribution, in particular the excess in the Galactic bulge, remains difficult to explain. Additionally, one of the largest uncertainties in these studies is the unknown distance that positrons propagate before annihilation. In this paper, we will summarize the current knowledge base of Galactic positrons, and discuss how next-generation instruments could finally provide the answers.Non peer reviewedFinal Accepted Versio

Herschel/PACS far-infrared photometry of two z>4 quasars

We present Herschel far-infrared (FIR) observations of two sub-mm bright quasars at high redshift: SDSS J1148+5251 (z=6.42) and BR 1202-0725 (z=4.69) obtained with the PACS instrument. Both objects are detected in the PACS photometric bands. The Herschel measurements provide additional data points that constrain the FIR spectral energy distributions (SEDs) of both sources, and they emphasise a broad range of dust temperatures in these objects. For lambda_rest ~< 20mu, the two SEDs are very similar to the average SEDs of quasars at low redshift. In the FIR, however, both quasars show excess emission compared to low-z QSO templates, most likely from cold dust powered by vigorous star formation in the QSO host galaxies. For SDSS J1148+5251 we detect another object at 160mu with a distance of ~10 arcseconds from the QSO. Although no physical connection between the quasar and this object can be shown with the available data, it could potentially confuse low-resolution measurements, thus resulting in an overestimate of the FIR luminosity of the z=6.42 quasar.Comment: 4 pages, 3 figures, accepted for publication in the A&A special issue on Hersche

Antiparasitic Constituents of Beilschmiedia louisii and Beilschmiedia obscura and Some Semisynthetic Derivatives (Lauraceae)

Waleguele CC, Mba’ning BM, Awantu AF, et al. Antiparasitic Constituents of Beilschmiedia louisii and Beilschmiedia obscura and Some Semisynthetic Derivatives (Lauraceae). Molecules. 2020;25(12): 2862.The MeOH/CH2Cl2 (1:1) extracts of the roots and leaves of Beilschmiedia louisii and B. obscura showed potent antitrypanosomal activity during preliminary screening on Trypanosoma brucei brucei. Phytochemical investigation of these extracts led to the isolation of a mixture of two new endiandric acid derivatives beilschmiedol B (1) and beilschmiedol C (2), and one new phenylalkene obscurene A (3) together with twelve known compounds (4–15). In addition, four new derivatives (11a–11d) were synthesized from compound 11. Their structures were elucidated based on their NMR and MS data. Compounds 5, 6, and 7 were isolated for the first time from the Beilschmiedia genus. Additionally, the NMR data of compound 4 are given here for the first time. The isolates were evaluated for their antitrypanosomal and antimalarial activities against Tb brucei and the Plasmodium falciparum chloroquine-resistant strain Pf3D7 in vitro, respectively. From the tested compounds, the mixture of new compounds 1 and 2 exhibited the most potent antitrypanosomal activity in vitro with IC50 value of 4.91 μM

The Photodetector Array Camera and Spectrometer (PACS) on the Herschel Space Observatory

The Photodetector Array Camera and Spectrometer (PACS) is one of the three science instruments on ESA's far infrared and submillimetre observatory. It employs two Ge:Ga photoconductor arrays (stressed and unstressed) with 16x25 pixels, each, and two filled silicon bolometer arrays with 16x32 and 32x64 pixels, respectively, to perform integral-field spectroscopy and imaging photometry in the 60-210\mu\ m wavelength regime. In photometry mode, it simultaneously images two bands, 60-85\mu\ m or 85-125\mu\m and 125-210\mu\ m, over a field of view of ~1.75'x3.5', with close to Nyquist beam sampling in each band. In spectroscopy mode, it images a field of 47"x47", resolved into 5x5 pixels, with an instantaneous spectral coverage of ~1500km/s and a spectral resolution of ~175km/s. We summarise the design of the instrument, describe observing modes, calibration, and data analysis methods, and present our current assessment of the in-orbit performance of the instrument based on the Performance Verification tests. PACS is fully operational, and the achieved performance is close to or better than the pre-launch predictions

Parity Detection of Propagating Microwave Fields

The parity of the number of elementary excitations present in a quantum system provides important insights into its physical properties. Parity measurements are used, for example, to tomographically reconstruct quantum states or to determine if a decay of an excitation has occurred, information which can be used for quantum error correction in computation or communication protocols. Here we demonstrate a versatile parity detector for propagating microwaves, which distinguishes between radiation fields containing an even or odd number n of photons, both in a single-shot measurement and without perturbing the parity of the detected field. We showcase applications of the detector for direct Wigner tomography of propagating microwaves and heralded generation of Schr\"odinger cat states. This parity detection scheme is applicable over a broad frequency range and may prove useful, for example, for heralded or fault-tolerant quantum communication protocols

Charged Higgs- and R-Parity-Violating Slepton-Strahlung at Hadron Colliders

It is shown that the radiation of a charged Higgs boson off a third-generation quark (charged-Higgs-strahlung) provides an important channel for the discovery of the charged Higgs at hadron colliders. Equivalently, in supersymmetric models with explicit lepton-number (R-parity) violation, sleptons may also be produced in association with quarks (slepton-strahlung). Higgs- and slepton-strahlung production cross sections are given for both the Tevatron and the LHC. The LHC cross sections imply that heavy ${\cal{O}}$(TeV) charged Higgs bosons can be produced via charged-Higgs-strahlung and that strahlung production of charged sleptons is possible even for small R-parity violating couplings. The possible discovery of sleptons through this channel offers a surprising handle on models of neutrino masses.Comment: 23 pages, LaTex + RevTex, 11 figures (included). Title modified. (Published version.