Osteocyte-Driven Downregulation of Snail Restrains Effects of Drd2 Inhibitors on Mammary Tumor Cells

While bone is a frequent target of breast cancer-associated metastasis, little is known about the effects of tumor-bone interactions on the efficacy of tumor-suppressing agents. Here we examined the effect of two FDA-approved dopamine modulators, fluphenazine and trifluoperazine, on mammary tumor cells, osteoclasts, osteoblasts, and osteocytes. These agents suppressed proliferation and migration of mammary tumor cells chiefly by antagonizing dopamine receptor D2 and reduced bone resorption by downregulating nuclear factor of activated T cells, cytoplasmic 1 (Nfatc1). Three-dimensional spheroid formation assays revealed that tumor cells have high affinity to osteocytes and type I collagen, and interactions with osteocytes as well as administration of fluphenazine and trifluoperazine downregulated Snail and suppressed migratory behaviors. Unlike the inhibitory action of fluphenazine and trifluoperazine on tumor growth, tumor-osteocyte interactions stimulated tumor proliferation by upregulating NFκB and Akt. In the bone microenvironment, osteocytes downregulated Snail and acted as an attractant as well as a stimulant to mammary tumor cells. These results demonstrate that tumor-osteocyte interactions strengthen dopamine receptor-mediated suppression of tumor migration but weaken its inhibition of tumor proliferation in the osteocyte-rich bone microenvironment.Significance: These findings provide novel insight into the cellular cross-talk in the bone microevironment and the effects of dopamine modulators on mammary tumor cells and osteocytes. Cancer Res; 78(14); 3865-76. ©2018 AACR

Three dimensional integration technology using copper wafer bonding

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2006.Includes bibliographical references (p. 216-219).With 3-D integration, the added vertical component could theoretically increase the device density per footprint ratio of a given chip by n-fold, provide a means of heterogeneous integration of devices fabricated from different technologies, and reduce the global RC delay to a non-factor in circuits by using smarter 3-D CAD tools for optimizing device placement. This thesis work will focus primarily on the development and realization of a viable 3-D flow fabricated within MTL. Specifically, the presentation will attempt on answering these questions in regards to 3-D: 1. What enabling technologies were needed for 3-D to work ? 2. Does it really work ? 3. Will the "3-D heat dissipation problem" prevent it from working ? 4. What applications is it good for ? Referring to the first item, a viable 3-D integration flow has been developed on both the wafer-and-die-level, and the enabling technologies were the following: Low temperature Cu-Cu thermocompression bonding, an aluminum-Cu based temporary laminate structure used stabilizing the handle wafer - SOI wafer bond, and tooling optimization of the die-die bonder setup in TRL.(cont.,) Next, nominal feasibility of the 3-D flow was demonstrated by fabricating a 21-stage and 43-stage CMOS ring oscillators, where each single CMOS inverter / buffer stage was constructed by connecting NMOS-only devices from one substrate with PMOS-only devices from a separate substrate. Proof-of-concept was accomplished when all 92 Cu-Cu bonds, 204 thru-SOI Cu damascene vias, and 56 pairs of MOSFETs communicated simultaneously to produce a 2.75 MHz (43-stage) and 5.5 MHz (21-stage) oscillators, ringing rail-to-rail at 5 V Vdd under proper Vt adjustments on the SOI-PMOS using integrated backgates. Furthermore, to combat the perceived heat dissipation problem in 3-D, this work focused on using the Cu-Cu interlayer bond as heat dissipators, with Cu planes working as flux spreaders and Cu vias as direct heat conduits. Finally, 3-D RF passive integration onto existing chips can be made feasible, under certain device performance trade-offs, by using cobalt magnetic shielding, which offers at least a -10 dB throughout 0-20 GHz, with a max isolation of -24 dB at 13 GHz, at +4 dBm reference input power.by Andy Fan.Ph.D

Investigation of the Sources of Variability in the Wurster Coater: Analysis of Particle Cycle Times using PEPT

Positron Emission Particle Tracking (PEPT) has been used successfully to study pellet motion within the Wurster coater. PEPT experiments were undertaken to understand how the parameters of batch size and partition gap interact with each other; and to determine their effects on the particle cycle time and the components of the particle cycle time: the flight and annulus times and their respective distributions. This enabled the determination of optimum operating conditions for a given set of process conditions

Fast Pyrolysis of Biomass in a Circulating Fluidised Bed

CFB biomass pyrolysis produces mostly bio-oil. Reaction rates are fast (k \u3e 0.5 s-1). Yields exceed 60 wt% of bio-oil at 500 °C and at a residence time for oil and char t \u3c 2.5 s. as achieved in plug flow CFB-mode, shown by PEPT to occur at U \u3e (Utr + 1) m/s and G \u3e 200 kg/m² s

Quantum synchronization effects induced by strong nonlinearities

A paradigm for quantum synchronization is the quantum analog of the Stuart--Landau oscillator, which corresponds to a van der Pol oscillator in the limit of weak (i.e. vanishingly small) nonlinearity. Due to this limitation, the quantum Stuart--Landau oscillator fails to capture interesting nonlinearity-induced phenomena such as relaxation oscillations. To overcome this deficiency we propose an alternative model which approximates the van der Pol oscillator to finitely large nonlinearities while remaining numerically tractable. This allows us to uncover interesting phenomena in the deep-quantum strongly-nonlinear regime with no classical analog, such as the persistence of amplitude death on resonance. We also report nonlinearity-induced position correlations in reactively coupled quantum oscillators. Such coupled oscillations become more and more correlated with increasing nonlinearity before reaching some maximum. Again, this behavior is absent classically. We also show how strong nonlinearity can enlarge the synchronization bandwidth in both single and coupled oscillators. This effect can be harnessed to induce mutual synchronization between two oscillators initially in amplitude death.Comment: 6 pages, 3 figure

Method for the elucidation of LAMP products captured on lateral flow strips in a point of care test for HPV 16

Loop-mediated amplification (LAMP) is an isothermal amplification technique favored in diagnostics and point-of-care work due to its high sensitivity and ability to run in isothermal conditions. In addition, a visual readout by lateral flow strips (LFS) can be used in conjunction with LAMP, making the assay accessible at the point-of-care. However, the amplicons resulting from a LAMP reaction varied in length and shape, making them undiscernible on a double-stranded DNA intercalating dye stained gel. Standard characterization techniques also do not identify which amplicons specifically bind to the LFS, which generate the visual readout. We aimed to standardize our characterization of LAMP products during assay development by using fluorescein amidite (FAM) and biotin-tagged loop forward and backward primers during assay development. A pvuII restriction enzyme digest is applied to the LAMP products. FAM-tagged bands are directly correlated with the LFS visual readout. We applied this assay development workflow for an HPV 16 assay using both plasmid DNA and clinical samples to demonstrate proof of concept for generalized assay development work.U54 EB015408 - NIBIB NIH HHS; UL1 TR001430 - NCATS NIH HHS; NIH U54 EB015408 - NIH Point of Care Technology Research Network (POCTRN)Accepted manuscrip

How do tree species with different successional stages affect soil organic nitrogen transformations?

Organic nitrogen (N) is the most important N component of soil organic matter.However, knowledge on how tree species with different successional stages affect its transformations in soils remains limited. To address this issue, we sampled mineral soils (0−10 cm) in monocultures composed by tree species of different successional stages, including early (black alder and silver birch), early to mid (sycamore and European ash), and late (sweet chestnut, pedunculate oak and European beech), and measured the potential protease activity, the microbial uptake and respiration of 14C-labeled organic N (L-alanine and L-trialanine), and the mineralization of L-alanine N. The activities of alanine aminopeptidase and leucine aminopeptidase (153.8−341.9 and 91.6−147.9 nmol/g/h, respectively), the half-life of the uptake of alanine and trialanine (26.7−39.6 and 60.8−78.6 min, respectively), the half-life of the mineraliztion of alanine and trialanine (1.98−2.45 and 2.98−4.13 h, respectively) by soil microbes were altered by tree species of different successional stages, systematically changing the transformation chain of soil organic N. From trees of early successional stage to that of late, the turnover rates of soil organic N appeared to decrease and the half-life appeared to increase significantly. The (carbon) C:N ratio of soil microbial biomass was positively related to the half-life of 14Clabeled alanine and trialanine mineralization, and was negatively related to the C use efficiency of alanine, suggesting that microbial demand for C could partially drive the assimilation of soil organic N. Our results suggest that the successional stage of tree species play an important role in regulating the soil organic N turnover. An improved understanding of how tree species with different successional stages influence microbial function and soil organic N cycling is beneficial to future afforestation and forest management, alleviating the impacts of global change on the ecosystem