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At least 37 records · Page 2

PIPER Continuous Adiabatic Demagnetization Refrigerator

We report upon the development and testing of a 4-stage adiabatic demagnetization refrigerator (ADR) capable of continuous cooling at 0.100 Kelvin. This cooler is being built to cool the detector array aboard NASA's Primordial Inflation Polarization Explorer (PIPER) observatory. The goal of this balloon mission is to measure the primordial gravitational waves that should exist if the theory of cosmological inflation is correct. At altitude, the ADR will hold the array of transition-edge sensors at 100 mK continuously while periodically rejecting heat to a 1.2 K pumped helium bath. During testing on ground, the array is held at the same temperature but heat is rejected to a 4.2 K helium bath indicating the flexibility in this coolers design.

Magnetic Cooling Sub-Kelvin ADR↗

PIPER: Performance Insight for Programmers and Exascale Runtimes (Final Technical Report)

This project concentrated on the development of novel performance tools and analysis techniques for large scale parallel systems and applications, eventually targeting exascale platforms. Activities conducted included work to novel root cause detection approaches and an auto-tuning framework for parallel systems. The work has led to several software solutions, which are available as open source.

97 MATHEMATICS AND COMPUTING↗

A Focus on Cryogenic Engineering for the Primordial Inflation Polarization Explorer (PIPER) Mission

Cryogenic engineering involves design and modification of equipment that is used under boiling point of nitrogen which is 77 K. The focus of this paper will be on the design of hardware for cryogenic use and a retrofit that was done to the main laboratory cryostat used to test flight components for the Primordial Inflation Polarization Explorer balloon-borne mission. Data from prior tests showed that there was a superfluid helium leak and a total disassemble of the cryostat was conducted in order to localize and fix the leak. To improve efficiency new fill tubes and clamps with modifications were added to the helium tank. Upon removal of the tank, corrosion was found on the flange face that connects to the helium cold plate and therefore had to be fully replaced and copper plated to prevent future corrosion. Indium seals were also replaced for the four fill tubes, a helium level sensor, and the nitrogen and helium tanks. Four additional shielded twisted pairs of cryogenic wire and a wire harness for the Superconducting Quantum Interference Devices (SQUIDs) were added. Finally, there was also design work done for multiple pieces that went inside the cryostat and a separate probe used to test the SQUIDs. Upon successful completion of the cryostat upgrade, tests were run to check the effectiveness and stability of the upgrades. The post-retrofit tests showed minor leaks were still present and due to this, superfluidity has still not been attained. As such there could still be a possibility of a superfluid leak appearing in the future. Regardless, the copper plating on the helium tank has elongated the need to service it by three to five years.

Rosas, Rogelio↗

Airborne antenna pattern calculations

Calculated principal-and off-principal plane patterns are presented for the following aircraft: de Havilland DHC-7, Rockwell Sabreliner 75A, Piper PA-31T Cheyenne, Lockheed Jet Star II, Piper PA-31-350 Navajo Chieftain, Beechcraft Duke B60, Rockwell Commander 700, Cessna Citation 3, Piper PA-31P Pressurized Navajo, Lear Jet, and Twin Otter DHC-6.

Knerr, T. J.↗

TU-CD-BRA-04: Evaluation of An Atlas-Based Segmentation Method for Prostate and Peripheral Zone Regions On MRI

Purpose: Prostate MRI plays an important role in diagnosis, biopsy guidance, and therapy planning for prostate cancer. Prostate MRI contours can be used to aid in image fusion for ultrasound biopsy guidance and delivery of radiation. Our goal in this study is to evaluate an automatic atlas-based segmentation method for generating prostate and peripheral zone (PZ) contours on MRI. Methods: T2-weighted MRIs were acquired on 3T-Discovery MR750 System (GE, Milwaukee). The Volumes of Interest (VOIs): prostate and PZ were outlined by an expert radiation oncologist and used to create an atlas library for atlas-based segmentation. The atlas-segmentation accuracy was evaluated using a leave-one-out analysis. The method involved automatically finding the atlas subject that best matched the test subject followed by a normalized intensity-based free-form deformable registration of the atlas subject to the test subject. The prostate and PZ contours were transformed to the test subject using the same deformation. For each test subject the three best matches were used and the final contour was combined using Majority Vote. The atlas-segmentation process was fully automatic. Dice similarity coefficients (DSC) and mean Hausdorff values were used for comparison. Results: VOIs contours were available for 28 subjects. For the prostate, the atlas-based segmentation method resulted in an average DSC of 0.88+/−0.08 and a mean Hausdorff distance of 1.1+/−0.9mm. The number of patients (#) in DSC ranges are as follows: 0.60–0.69(1), 0.70–0.79(2), 0.80–0.89(13), >0.89(11). For the PZ, the average DSC was 0.72+/−0.17 and average Hausdorff of 0.9+/−0.9mm. The number of patients (#) in DSC ranges are as follows: <0.60(4), 0.60–0.69(6), 0.70–0.79(7), 0.80–0.89(9), >0.89(1). Conclusion: The MRI atlas-based segmentation method achieved good results for both the whole prostate and PZ compared to expert defined VOIs. The technique is fast, fully automatic, and has the potential to provide significant time savings for prostate VOI definition. AS Nelson and J Piper are partial owners of MIM Software, Inc. AS Nelson, J Piper, K Curry, and A Swallen are current employees at MIM Software, Inc.

60 APPLIED LIFE SCIENCES↗

Elucidating Drought-Tolerance Mechanisms in Plant Roots through 1H NMR Metabolomics in Parallel with MALDI-MS, and NanoSIMS Imaging Techniques

As direct mediators between plants and soil, roots play an important role in metabolic responses to environmental stresses such as drought, yet these responses are vastly uncharacterized on a plant-specific level, especially for co-occurring species. Here, we aim to examine the effects of drought on root metabolic profiles and carbon allocation pathways of three tropical rainforest species by combining cutting-edge metabolomic and imaging technologies in an in situ position-specific 13C-pyruvate root-labeling experiment. Further, washed (rhizosphere-depleted) and unwashed roots were examined to test the impact of microbial presence on root metabolic pathways. Drought had a species-specific impact on the metabolic profiles and spatial distribution in Piper sp. and Hibiscus rosa sinensis roots, signifying different defense mechanisms; Piper sp. enhanced root structural defense via recalcitrant compounds including lignin, while H. rosa sinensis enhanced biochemical defense via secretion of antioxidants and fatty acids. In contrast, Clitoria fairchildiana, a legume tree, was not influenced as much by drought but rather by rhizosphere presence where carbohydrate storage was enhanced, indicating a close association with symbiotic microbes. This study demonstrates how multiple techniques can be combined to identify how plants cope with drought through different drought-tolerance strategies and the consequences of such changes on below-ground organic matter composition.

Drought, Carbon cycle, MALDI-MSI, Metabolomics, Na↗

Primordial Inflation Polarization Explorer: Status and Plans

The Primordial Inflation Polarization Explorer is a balloon-borne instrument to measure the polarization of the cosmic microwave background in order to detect the characteristic signature of gravity waves created during an inflationary epoch in the early universe. PIPER combines cold /I.G K\ optics, 5120 bolometric detectors, and rapid polarization modulation using VPM grids to achieve both high sensitivity and excellent control of systematic errors. I will discuss the current status and plans for the PIPER instrument.

Kogut, Alan↗

Variable-Delay Polarization Modulators for Cryogenic Millimeter-Wave Applications

We describe the design, construction, and initial validation of the variable-delay polarization modulator (VPM) designed for the PIPER cosmic microwave background polarimeter. The VPM modulates between linear and circular polarization by introducing a variable phase delay between orthogonal linear polarizations. Each VPM has a diameter of 39 cm and is engineered to operate in a cryogenic environment (1.5 K). We describe the mechanical design and performance of the kinematic double-blade flexure and drive mechanism along with the construction of the high precision wire grid polarizers.

cryogenic environment↗

Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling

Highlights: Black-Right-Pointing-Pointer Anti-atherogenic effect of PL was examined using partial carotid ligation model in ApoE KO mice. Black-Right-Pointing-Pointer PL prevented atherosclerotic plaque development, VSMCs proliferation, and NF-{kappa}B activation. Black-Right-Pointing-Pointer Piperlongumine reduced vascular smooth muscle cell activation through PDGF-R{beta} and NF-{kappa}B-signaling. Black-Right-Pointing-Pointer PL may serve as a new therapeutic molecule for atherosclerosis treatment. -- Abstract: Piperlongumine (piplartine, PL) is an alkaloid found in the long pepper (Piper longum L.) and has well-documented anti-platelet aggregation, anti-inflammatory, and anti-cancer properties; however, the role of PL in prevention of atherosclerosis is unknown. We evaluated the anti-atherosclerotic potential of PL in an in vivo murine model of accelerated atherosclerosis and defined its mechanism of action in aortic vascular smooth muscle cells (VSMCs) in vitro. Local treatment with PL significantly reduced atherosclerotic plaque formation as well as proliferation and nuclear factor-kappa B (NF-{kappa}B) activation in an in vivo setting. PL treatment in VSMCs in vitro showed inhibition of migration and platelet-derived growth factor BB (PDGF-BB)-induced proliferation to the in vivo findings. We further identified that PL inhibited PDGF-BB-induced PDGF receptor beta activation and suppressed downstream signaling molecules such as phospholipase C{gamma}1, extracellular signal-regulated kinases 1 and 2 and Akt. Lastly, PL significantly attenuated activation of NF-{kappa}B-a downstream transcriptional regulator in PDGF receptor signaling, in response to PDGF-BB stimulation. In conclusion, our findings demonstrate a novel, therapeutic mechanism by which PL suppresses atherosclerosis plaque formation in vivo.

60 APPLIED LIFE SCIENCES↗

Piperlongumine inhibits LMP1/MYC-dependent mouse B-lymphoma cells

Highlights: •Mouse model of human Burkitt lymphoma revealed cancer inhibition by PL. •Treatment with PL led to apoptosis of malignant but not normal B cells. •PL inhibited LMP1–NF-κB–Myc-dependent target genes including p21-encoding Cdkn1a. •PL holds promise for new interventions approaches to hematologic malignancies. -- Abstract: Piperlongumine (PL), isolated from the fruit of Long pepper, Piper longum, is a cancer-inhibiting compound that selectively kills tumor cells while sparing their normal counterparts. Here we evaluated the efficacy with which PL suppresses malignant B cells derived from a newly developed, double-transgenic mouse model of human endemic Burkitt lymphoma (BL), designated mCD40-LMP1/iMyc{sup Eμ}. PL inhibited tumor cell proliferation in a concentration-dependent manner and induced apoptosis of neoplastic but not normal B cells. Treatment with PL resulted in downregulation of EBV-encoded LMP1, cellular Myc, constitutive NF-κB activity, and a host of LMP1-Myc-NF-κB-regulated target genes including Aurka, Bcat1, Bub1b, Ccnb1, Chek1, Fancd2, Tfrc and Xrcc6. Of note, p21{sup Cip1}-encoding Cdkn1a was suppressed independent of changes in Trp53 mRNA levels and p53 DNA-binding activity. Considering the central role of the LMP1–NF-κB–Myc axis in B-lineage neoplasia, these findings further our understanding of the mechanisms by which PL inhibits B-lymphoma and provide a preclinical rationale for the inclusion of PL in new interventions in blood cancers.

60 APPLIED LIFE SCIENCES↗

Piperlongumine inhibits the proliferation and survival of B-cell acute lymphoblastic leukemia cell lines irrespective of glucocorticoid resistance

Highlights: • PL inhibits the proliferation of B-ALL cell lines irrespective of GC-resistance. • PL selectively kills B-ALL cells by increasing ROS, but not normal counterpart. • PL does not sensitize majority of B-ALL cells to DEX. • PL represses the network of constitutively activated TFs and modulates their target genes. • PL may serve as a new therapeutic molecule for GC-resistant B-ALL. - Abstract: Piperlongumine (PL), a pepper plant alkaloid from Piper longum, has anti-inflammatory and anti-cancer properties. PL selectively kills both solid and hematologic cancer cells, but not normal counterparts. Here we evaluated the effect of PL on the proliferation and survival of B-cell acute lymphoblastic leukemia (B-ALL), including glucocorticoid (GC)-resistant B-ALL. Regardless of GC-resistance, PL inhibited the proliferation of all B-ALL cell lines, but not normal B cells, in a dose- and time-dependent manner and induced apoptosis via elevation of ROS. Interestingly, PL did not sensitize most of B-ALL cell lines to dexamethasone (DEX). Only UoC-B1 exhibited a weak synergistic effect between PL and DEX. All B-ALL cell lines tested exhibited constitutive activation of multiple transcription factors (TFs), including AP-1, MYC, NF-κB, SP1, STAT1, STAT3, STAT6 and YY1. Treatment of the B-ALL cells with PL significantly downregulated these TFs and modulated their target genes. While activation of AURKB, BIRC5, E2F1, and MYB mRNA levels were significantly downregulated by PL, but SOX4 and XBP levels were increased by PL. Intriguingly, PL also increased the expression of p21 in B-ALL cells through a p53-independent mechanism. Given that these TFs and their target genes play critical roles in a variety of hematological malignancies, our findings provide a strong preclinical rationale for considering PL as a new therapeutic agent for the treatment of B-cell malignancies, including B-ALL and GC-resistant B-ALL.

60 APPLIED LIFE SCIENCES↗

Uncovering the dominant role of root metabolism in shaping rhizosphere metabolome under drought in tropical rainforest plants

Plant-soil-microbe interactions are crucial for driving rhizosphere processes that contribute to metabolite turnover and nutrient cycling. With the increasing frequency and severity of water scarcity due to climate warming, understanding how plant-mediated processes, such as root exudation, influence soil organic matter turnover in the rhizosphere is essential. In this study, we used 16S rRNA gene amplicon sequencing, rhizosphere metabolomics, and position-specific 13 C-pyruvate labeling to examine the effects of three different plant species (Piper auritum, Hibiscus rosa sinensis, and Clitoria fairchildiana) and their associated microbial communities on soil organic carbon turnover in the rhizosphere. Here, our findings indicate that in these tropical plants, the rhizosphere metabolome is primarily shaped by the response of roots to drought rather than direct shifts in the rhizosphere bacterial community composition. Specifically, the reduced exudation of plant roots had a notable effect on the metabolome of the rhizosphere of P. auritum, with less reliance on neighboring microbes. Contrary to P. auritum, H. rosa sinensis and C. fairchildiana experienced changes in their exudate composition during drought, causing alterations to the bacterial communities in the rhizosphere. This, in turn, had a collective impact on the rhizosphere's metabolome. Furthermore, the exclusion of phylogenetically distant microbes from the rhizosphere led to shifts in its metabolome. Additionally, C. fairchildiana appeared to be associated with only a subset of symbiotic bacteria under drought conditions. These results indicate that plant species-specific microbial interactions systematically change with the root metabolome. As roots respond to drought, their associated microbial communities adapt, potentially reinforcing the drought tolerance strategies of plant roots. These findings have significant implications for maintaining plant health and preference during drought stress and improving plant performance under climate change.

54 ENVIRONMENTAL SCIENCES↗

Hydroxychavicol, a betel leaf component, inhibits prostate cancer through ROS-driven DNA damage and apoptosis

Dietary phytochemicals are excellent ROS-modulating agents and have been shown to effectively enhance ROS levels beyond toxic threshold in cancer cells to ensure their selective killing while leaving normal cells unscathed. Here we demonstrate that hydroxychavicol (HC), extracted and purified from Piper betel leaves, significantly inhibits growth and proliferation via ROS generation in human prostate cancer, PC-3 cells. HC perturbed cell-cycle kinetics and progression, reduced clonogenicity and mediated cytotoxicity by ROS-induced DNA damage leading to activation of several pro-apoptotic molecules. In addition, HC treatment elicited a novel autophagic response as evidenced by the appearance of acidic vesicular organelles and increased expression of autophagic markers, LC3-IIb and beclin-1. Interestingly, quenching of ROS with tiron, an antioxidant, offered significant protection against HC-induced inhibition of cell growth and down regulation of caspase-3, suggesting the crucial role of ROS in mediating cell death. The collapse of mitochondrial transmembrane potential by HC further revealed the link between ROS generation and induction of caspase-mediated apoptosis in PC-3 cells. Our data showed remarkable inhibition of prostate tumor xenografts by ∼ 72% upon daily oral administration of 150 mg/kg bw HC by quantitative tumor volume measurements and non-invasive real-time bioluminescent imaging. HC was well-tolerated at this dosing level without any observable toxicity. This is the first report to demonstrate the anti-prostate cancer efficacy of HC in vitro and in vivo, which is perhaps attributable to its selective prooxidant activity to eliminate cancer cells thus providing compelling grounds for future preclinical studies to validate its potential usefulness for prostate cancer management. - Highlights: • HC perturbs cell-cycle progression by induction of reactive oxygen species (ROS). • HC mediated cytotoxicity by ROS-induced DNA damage leading to apoptosis. • HC induced ROS-mediated autophagic response. • It inhibited prostate tumor growth by ∼ 72% without any observable toxicity. • Its anticancer efficacy is likely due to its selective prooxidant activity.

60 APPLIED LIFE SCIENCES↗

Detection of irradiated spices using photo-stimulated luminescence technique (PSL)

Photo-stimulated luminescence (PSL) technique was applied to detect irradiated black pepper (Piper nigrum), cinnamon (Cinnamomum verum) and turmeric (Curcuma longa) after dark storage for 1 day, 3 and 6 months. Using screening and calibrated PSL, all samples were correctly discriminated between non-irradiated and spices irradiated with doses 1, 5 and 10 kGy. The PSL photon counts (PCs) of irradiated spices increased with increasing dose, with turmeric showing highest sensitivity index to irradiation compared to black pepper and cinnamon. The differences in response are possibly attributed to the varying quantity and quality of silicate minerals present in each spice sample. PSL signals of all irradiated samples reduced after 3 and 6 months storage. The results of this study provide a useful database on the applicability of PSL technique for the detection of Malaysian irradiated spices.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Robust forecasts on fundamental physics from the foreground-obscured, gravitationally-lensed CMB polarization

Recent results from the BICEP, Keck Array and Planck Collaborations demonstrate that Galactic foregrounds are an unavoidable obstacle in the search for evidence of inflationary gravitational waves in the cosmic microwave background (CMB) polarization. Beyond the foregrounds, the effect of lensing by intervening large-scale structure further obscures all but the strongest inflationary signals permitted by current data. With a plethora of ongoing and upcoming experiments aiming to measure these signatures, careful and self-consistent consideration of experiments' foreground- and lensing-removal capabilities is critical in obtaining credible forecasts of their performance. We investigate the capabilities of instruments such as Advanced ACTPol, BICEP3 and Keck Array, CLASS, EBEX10K, PIPER, Simons Array, SPT-3G and SPIDER, and projects as COrE+, LiteBIRD-ext, PIXIE and Stage IV, to clean contamination due to polarized synchrotron and dust from raw multi-frequency data, and remove lensing from the resulting co-added CMB maps (either using iterative CMB-only techniques or through cross-correlation with external data). Incorporating these effects, we present forecasts for the constraining power of these experiments in terms of inflationary physics, the neutrino sector, and dark energy parameters. Made publicly available through an online interface, this tool enables the next generation of CMB experiments to foreground-proof their designs, optimize their frequency coverage to maximize scientific output, and determine where cross-experimental collaboration would be most beneficial. We find that analyzing data from ground, balloon and space instruments in complementary combinations can significantly improve component separation performance, delensing, and cosmological constraints over individual datasets. In particular, we find that a combination of post-2020 ground- and space-based experiments could achieve constraints such as σ(r)∼1.3×10{sup −4}, σ(n{sub t})∼0.03, σ( n{sub s} )∼1.8×10{sup −3}, σ(α{sub s})∼1.7×10{sup −3}, σ( M{sub ν} )∼31 meV, σ( w )∼0.09, σ( w{sub 0} )∼ 0.25, 0σ( w{sub a} )∼ 0.5, σ( N{sub eff} )∼0.024 and σ( Ω{sub k} )∼1.5×10{sup −3}, after component separation and iterative delensing.

79 ASTRONOMY AND ASTROPHYSICS↗