A Three Dimensional Lattice of Ion Traps

We propose an ion trap configuration such that individual traps can be stacked together in a three dimensional simple cubic arrangement. The isolated trap as well as the extended array of ion traps are characterized for different locations in the lattice, illustrating the robustness of the lattice of traps concept. Ease in the addressing of ions at each lattice site, individually or simultaneously, makes this system naturally suitable for a number of experiments. Application of this trap to precision spectroscopy, quantum information processing and the study of few particle interacting system are discussed.Comment: 4 pages, 4 Figures. Fig 1 appears as a composite of 1a, 1b, 1c and 1d. Fig 2 appears as a composite of 2a, 2b and 2

Targeting quiescent leukemic stem cells using second generation autophagy inhibitors

In chronic myeloid leukemia (CML), tyrosine kinase inhibitor (TKI) treatment induces autophagy that promotes survival and TKI-resistance in leukemic stem cells (LSCs). In clinical studies hydroxychloroquine (HCQ), the only clinically approved autophagy inhibitor, does not consistently inhibit autophagy in cancer patients, so more potent autophagy inhibitors are needed. We generated a murine model of CML in which autophagic flux can be measured in bone marrow-located LSCs. In parallel, we use cell division tracing, phenotyping of primary CML cells, and a robust xenotransplantation model of human CML, to investigate the effect of Lys05, a highly potent lysosomotropic agent, and PIK-III, a selective inhibitor of VPS34, on the survival and function of LSCs. We demonstrate that long-term haematopoietic stem cells (LT-HSCs: Lin−Sca-1+c-kit+CD48−CD150+) isolated from leukemic mice have higher basal autophagy levels compared with non-leukemic LT-HSCs and more mature leukemic cells. Additionally, we present that while HCQ is ineffective, Lys05-mediated autophagy inhibition reduces LSCs quiescence and drives myeloid cell expansion. Furthermore, Lys05 and PIK-III reduced the number of primary CML LSCs and target xenografted LSCs when used in combination with TKI treatment, providing a strong rationale for clinical use of second generation autophagy inhibitors as a novel treatment for CML patients with LSC persistence

The origin of the split red clump in the Galactic bulge of the Milky Way

Near the minor axis of the Galactic bulge, at latitudes b < -5 degrees, the red giant clump stars are split into two components along the line of sight. We investigate this split using the three fields from the ARGOS survey that lie on the minor axis at (l,b) = (0,-5), (0,-7.5), (0,-10) degrees. The separation is evident for stars with [Fe/H] > -0.5 in the two higher-latitude fields, but not in the field at b = -5 degrees. Stars with [Fe/H] < -0.5 do not show the split. We compare the spatial distribution and kinematics of the clump stars with predictions from an evolutionary N-body model of a bulge that grew from a disk via bar-related instabilities. The density distribution of the peanut-shaped model is depressed near its minor axis. This produces a bimodal distribution of stars along the line of sight through the bulge near its minor axis, very much as seen in our observations. The observed and modelled kinematics of the two groups of stars are also similar. We conclude that the split red clump of the bulge is probably a generic feature of boxy/peanut bulges that grew from disks, and that the disk from which the bulge grew had relatively few stars with [Fe/H] < -0.5Comment: 12 pages, 9 figures, accepted for publication in Ap

Investigation of Anti-Relaxation Coatings for Alkali-Metal Vapor Cells Using Surface Science Techniques

Many technologies based on cells containing alkali-metal atomic vapor benefit from the use of anti-relaxation surface coatings in order to preserve atomic spin polarization. In particular, paraffin has been used for this purpose for several decades and has been demonstrated to allow an atom to experience up to 10,000 collisions with the walls of its container without depolarizing, but the details of its operation remain poorly understood. We apply modern surface and bulk techniques to the study of paraffin coatings, in order to characterize the properties that enable the effective preservation of alkali spin polarization. These methods include Fourier transform infrared spectroscopy, differential scanning calorimetry, atomic force microscopy, near-edge X-ray absorption fine structure spectroscopy, and X-ray photoelectron spectroscopy. We also compare the light-induced atomic desorption yields of several different paraffin materials. Experimental results include the determination that crystallinity of the coating material is unnecessary, and the detection of C=C double bonds present within a particular class of effective paraffin coatings. Further study should lead to the development of more robust paraffin anti-relaxation coatings, as well as the design and synthesis of new classes of coating materials.Comment: 12 pages, 12 figures. Copyright 2010 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in the Journal of Chemical Physics and may be found at http://link.aip.org/link/?JCP/133/14470

The in vitro effects of resistin on the innate immune signaling pathway in isolated human subcutaneous adipocytes

Context: Obesity-associated inflammation is a contributory factor in the pathogenesis of type 2 diabetes mellitus (T2DM); the mechanisms underlying the progression to T2DM are unclear. The adipokine resistin has demonstrated pro-inflammatory properties in relation to obesity and T2DM. Objective: To characterize resistin expression in human obesity and address the role of resistin in the innate immune pathway. Furthermore, examine the influence of lipopolysaccharide, recombinant human resistin (rhResistin), insulin and rosiglitazone in human adipocytes. Finally, analyze the effect of rhResistin on the expression of components of the NF-κB pathway and insulin signaling cascade. Methods: Abdominal subcutaneous adipose tissue was obtained from patients undergoing elective liposuction surgery (n = 35, aged: 36-49 yr; BMI: 26.5 ± 5.9 kg/m2). Isolated adipocytes were cultured with rhResistin (10-50 ng/ml). The level of cytokine secretion from isolated adipocytes was examined by ELISA. The effect of rhResistin on protein expression of components of the innate immune pathway was examined by Western blot. Results: In-vitro studies demonstrated that antigenic stimuli increase resistin secretion (P < 0.001) from isolated adipocytes. Pro-inflammatory cytokine levels were increased in response to rhResistin (P < 0.001); this was attenuated by rosiglitazone (P < 0.01). When examining components of the innate immune pathway, rhResistin stimulated Toll-like receptor-2 protein expression. Similarly, mediators of the insulin signaling pathway, phosphospecific JNK1 and JNK2, were upregulated in response to rhResistin. Conclusion: Resistin may participate in more than one mechanism to influence pro-inflammatory cytokine release from human adipocytes; potentially via the integration of NF-κB and JNK signaling pathways

Warehouse Commodity Classification from Fundamental Principles

Abstract In warehouse storage applications, it is important to classify the burning behavior of commodities and rank them according to their material flammability for early fire detection and suppression operations. In this study, a preliminary approach towards commodity classification is presented that models the early stage of large-scale warehouse fires by decoupling the problem into separate processes of heat and mass transfer. Two existing nondimensional parameters are used to represent the physical phenomena at the large-scale: a mass transfer number that directly incorporates the material properties of a fuel, and the soot yield of the fuel that controls the radiation observed in the large-scale. To facilitate modeling, a mass transfer number (or B-number) was experimentally obtained using mass-loss (burning rate) measurements from bench-scale tests, following from a procedure that was developed in Part I of this paper. Two fuels are considered: corrugated cardboard and polystyrene. Corrugated cardboard provides a source of flaming combustion in a warehouse and is usually the first item to ignite and sustain flame spread. Polystyrene is typically used as the most hazardous product in large-scale fire testing. The nondimensional mass transfer number was then used to model in-rack flame heights on 6.1 − 9.1 m (20 − 30 ft) stacks of &apos;C&apos; flute corrugated cardboard * Corresponding author Email address: [email protected] (K.J. Overholt) Preprint submitted to Fire Safety Journal January 11, 2011 boxes on rack-storage during the initial period of flame spread (involving flame spread over the corrugated cardboard face only). Good agreement was observed between the model and large-scale experiments during the initial stages of fire growth, and a comparison to previous correlations for in-rack flame heights is included

Phase 1b study of AVB-500 in combination with paclitaxel or pegylated liposomal doxorubicin platinum-resistant recurrent ovarian cancer

OBJECTIVE: GAS6 and AXL are expressed in high-grade serous ovarian cancer but not in normal ovarian tissue. AVB-500, a novel high affinity Fc-sAXL fusion protein, binds GAS6 preventing AXL signaling. This Phase 1b study (NCT03639246) evaluated safety, efficacy, and exploratory predictive markers of AVB-500 combined with paclitaxel (PAC) or pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer (PROC), and used a model informed drug development (MIDD) approach for identification of the recommended phase 2 dose (RP2D). METHODS: Eligible patients received AVB-500 at 10, 15, or 20 mg/kg IV q2wk combined with PAC (n = 23) or PLD (n = 30). Patients were treated until progression or unacceptable toxicity. All were followed for survival. RESULTS: No dose limiting toxicities were observed and serum GAS6 was completely suppressed across the three dose levels evaluated. AVB-500 + PAC yielded better clinical activity than AVB-500 + PLD with an ORR of 34.8% (8/23, 2 complete responses) and median DoR, PFS, and OS of 7.0, 3.1, and 10.3 months, respectively. Subgroup analyses showed AVB-500 + PAC patients who had no prior bevacizumab or whose AVB-500 trough levels were \u3e13.8 mg/L exhibited the best clinical response. The ORR and median PFS and OS in patients with these characteristics were ≥50%, ≥7.5 months, and ≥19 months, respectively. Given AVB-500 nor the combination with chemotherapy was expected to cause DLTs, the RP2D of AVB-500 was 15 mg/kg identified using an MIDD approach. CONCLUSION: AVB-500 was well-tolerated in combination with PAC or PLD and contributed to the clinical activity of PAC in PROC patients. Subgroup analyses identified a population of PROC patients who may benefit the most from AVB-500 treatment, which will be further assessed in an ongoing Phase 3 PROC trial

Deterministic delivery of externally cold and precisely positioned single molecular ions

We present the preparation and deterministic delivery of a selectable number of externally cold molecular ions. A laser cooled ensemble of Mg^+ ions subsequently confined in several linear Paul traps inter-connected via a quadrupole guide serves as a cold bath for a single or up to a few hundred molecular ions. Sympathetic cooling embeds the molecular ions in the crystalline structure. MgH^+ ions, that serve as a model system for a large variety of other possible molecular ions, are cooled down close to the Doppler limit and are positioned with an accuracy of one micrometer. After the production process, severely compromising the vacuum conditions, the molecular ion is efficiently transfered into nearly background-free environment. The transfer of a molecular ion between different traps as well as the control of the molecular ions in the traps is demonstrated. Schemes, optimized for the transfer of a specific number of ions, are realized and their efficiencies are evaluated. This versatile source applicable for broad charge-to-mass ratios of externally cold and precisely positioned molecular ions can serve as a container-free target preparation device well suited for diffraction or spectroscopic measurements on individual molecular ions at high repetition rates (kHz).Comment: 11 pages, 8 figure

Ultracold dense gas of deeply bound heteronuclear molecules

Recently, the quest for an ultracold and dense ensemble of polar molecules has attracted strong interest. Polar molecules have bright prospects for novel quantum gases with long-range and anisotropic interactions, for quantum information science, and for precision measurements. However, high-density clouds of ultracold polar molecules have so far not been produced. Here, we report a key step towards this goal. Starting from an ultracold dense gas of heteronuclear 40K-87Rb Feshbach molecules with typical binding energies of a few hundred kHz and a negligible dipole moment, we coherently transfer these molecules into a vibrational level of the ground-state molecular potential bound by >10 GHz. We thereby increase the binding energy and the expected dipole moment of the 40K-87Rb molecules by more than four orders of magnitude in a single transfer step. Starting with a single initial state prepared with Feshbach association, we achieve a transfer efficiency of 84%. While dipolar effects are not yet observable, the presented technique can be extended to access much more deeply bound vibrational levels and ultimately those exhibiting a significant dipole moment. The preparation of an ultracold quantum gas of polar molecules might therefore come within experimental reach.Comment: 5 pages, 5 figure

Multi-Target Prediction: A Unifying View on Problems and Methods

Multi-target prediction (MTP) is concerned with the simultaneous prediction of multiple target variables of diverse type. Due to its enormous application potential, it has developed into an active and rapidly expanding research field that combines several subfields of machine learning, including multivariate regression, multi-label classification, multi-task learning, dyadic prediction, zero-shot learning, network inference, and matrix completion. In this paper, we present a unifying view on MTP problems and methods. First, we formally discuss commonalities and differences between existing MTP problems. To this end, we introduce a general framework that covers the above subfields as special cases. As a second contribution, we provide a structured overview of MTP methods. This is accomplished by identifying a number of key properties, which distinguish such methods and determine their suitability for different types of problems. Finally, we also discuss a few challenges for future research