COP9 signalosome component JAB1/CSN5 is necessary for T cell signaling through LFA-1 and HIV-1 replication.

To determine critical host factors involved in HIV-1 replication, a dominant effector genetics approach was developed to reveal signaling pathways on which HIV-1 depends for replication. A large library of short peptide aptamers was expressed via retroviral delivery in T cells. Peptides that interfered with T cell activation-dependent processes that might support HIV-1 replication were identified. One of the selected peptides altered signaling, lead to a difference in T cell activation status, and inhibited HIV-1 replication. The target of the peptide was JAB1/CSN5, a component of the signalosome complex. JAB1 expression overcame the inhibition of HIV-1 replication in the presence of peptide and also promoted HIV-1 replication in activated primary CD4(+) T cells. This peptide blocked physiological release of JAB1 from the accessory T cell surface protein LFA-1, downstream AP-1 dependent events, NFAT activation, and HIV-1 replication. Thus, genetic selection for intracellular aptamer inhibitors of host cell processes proximal to signals at the immunological synapse of T cells can define unique mechanisms important to HIV-1 replication

Improvement of local Resistance of Safety-Related Structures and Reduction of Dynamic Response due to Missile Impact Loading

Evaluation of the load-bearing and shielding capacity of safety-related structures not designed for missile impact loading (e.g. from aircraft crash) led to problem-specific investigations, conducted with the aim of establishing effective shielding, reinforcing and energy dissipation concepts. To ensure protection of structures against missile impact, emphasis was placed in this study not only on upgrading the penetration resistance of the structures in the impacted area, but also in particular on reducing the dynamic response induced by impact loads. Although a number of shielding concepts exist which are useful in a theoretical sense, only a few of these are of any practical significance due to the rather small region affected by impact loading and the rather high magnitude of the loads. Any shielding concept suitable for protecting a building against the impact of a missile (e.g. aircraft) over its entire outer surface must provide the target with homogeneous protection in the form of a jacket of high strength and high energy dissipation capacity. Of the various concepts investigated, the most promising seems to be that providing protection by means of hollow-wall designs or special shielding elements, both made of energy-absorbing high-quality steel-fiberreinforced concrete [1]. This paper covers studies of different local design concepts for the targeted regions and material parameters which have a strong influence on the penetration resistance as well as energy dissipation capabilities of the impacted building. Possibilities for reinforcing the outer shells of typical buildings not originally designed to withstand missile impact are also presented

A compact and robust diode laser system for atom interferometry on a sounding rocket

We present a diode laser system optimized for laser cooling and atom interferometry with ultra-cold rubidium atoms aboard sounding rockets as an important milestone towards space-borne quantum sensors. Design, assembly and qualification of the system, combing micro-integrated distributed feedback (DFB) diode laser modules and free space optical bench technology is presented in the context of the MAIUS (Matter-wave Interferometry in Microgravity) mission. This laser system, with a volume of 21 liters and total mass of 27 kg, passed all qualification tests for operation on sounding rockets and is currently used in the integrated MAIUS flight system producing Bose-Einstein condensates and performing atom interferometry based on Bragg diffraction. The MAIUS payload is being prepared for launch in fall 2016. We further report on a reference laser system, comprising a rubidium stabilized DFB laser, which was operated successfully on the TEXUS 51 mission in April 2015. The system demonstrated a high level of technological maturity by remaining frequency stabilized throughout the mission including the rocket's boost phase

Integrated atomic quantum technologies in demanding environments: Development and qualification of miniaturized optical setups and integration technologies for UHV and space operation

Employing compact quantum sensors in field or in space (e.g., small satellites) implies demanding requirements on components and integration technologies. Within our work on integrated sensors, we develop miniaturized, ultra-stable optical setups for optical cooling and trapping of cold atomic gases. Besides challenging demands on alignment precision, and thermo-mechanical durability, we specifically address ultra-high vacuum (UHV) compatibility of our integration technologies and optical components. A prototype design of an UHV-compatible, crossed beam optical dipole trap setup and its application within a cold atomic quantum sensor is described. First qualification efforts on adhesive micro-integration technologies are presented. These tests are conducted in application-relevant geometries and material combinations common for micro-integrated optical setups. Adhesive aging will be investigated by thermal cycling or gamma radiation exposure. For vacuum compatibility testing, a versatile UHV testing system is currently being set up, enabling residual gas analysis and measurement of total gas rates down to 5•10-10mbar l/s at a base pressure of 10-11 mbar, exceeding the common ASTM E595 test

Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy.

The success of immunotherapy has led to a myriad of clinical trials accompanied by efforts to gain mechanistic insight and identify predictive signatures for personalization. However, many immune monitoring technologies face investigator bias, missing unanticipated cellular responses in limited clinical material. We present here a mass cytometry (CyTOF) workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. This assay enumerates ≥98% of peripheral immune cells with ≥4 positively identifying antigens. Robustness and reproducibility are demonstrated on multiple samples types, across two research centers and by orthogonal measurements. Using automated analysis, we identify stratifying immune signatures in bone marrow transplantation-associated graft-versus-host disease. Together, this validated workflow ensures comprehensive immunophenotypic analysis and data comparability and will accelerate biomarker discovery

BOOST -- A Satellite Mission to Test Lorentz Invariance Using High-Performance Optical Frequency References

BOOST (BOOst Symmetry Test) is a proposed satellite mission to search for violations of Lorentz invariance by comparing two optical frequency references. One is based on a long-term stable optical resonator and the other on a hyperfine transition in molecular iodine. This mission will allow to determine several parameters of the standard model extension in the electron sector up to two orders of magnitude better than with the current best experiments. Here, we will give an overview of the mission, the science case and the payload.Comment: 11 pages, 2 figures, accepted for publication in Phys. Rev.

Interferometry with Bose-Einstein Condensates in Microgravity

Atom interferometers covering macroscopic domains of space-time are a spectacular manifestation of the wave nature of matter. Due to their unique coherence properties, Bose-Einstein condensates are ideal sources for an atom interferometer in extended free fall. In this paper we report on the realization of an asymmetric Mach-Zehnder interferometer operated with a Bose-Einstein condensate in microgravity. The resulting interference pattern is similar to the one in the far-field of a double-slit and shows a linear scaling with the time the wave packets expand. We employ delta-kick cooling in order to enhance the signal and extend our atom interferometer. Our experiments demonstrate the high potential of interferometers operated with quantum gases for probing the fundamental concepts of quantum mechanics and general relativity.Comment: 8 pages, 3 figures; 8 pages of supporting materia

Microwave Assisted Synthesis of Py-Im Polyamides

Microwave synthesis was utilized to rapidly build Py-Im polyamides in high yields and purity using Boc-protection chemistry on Kaiser oxime resin. A representative polyamide targeting the 5′-WGWWCW-3′ (W = A or T) subset of the consensus Androgen and Glucocorticoid Response Elements was synthesized in 56% yield after 20 linear steps and HPLC purification. It was confirmed by Mosher amide derivatization of the polyamide that a chiral α-amino acid does not racemize after several additional coupling steps