Metabolic Dependencies in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal cancer with a long-term survival rate under 10%. Available cytotoxic chemotherapies have significant side effects, and only marginal therapeutic efficacy. FDA approved drugs currently used against PDA target DNA metabolism and DNA integrity. However, alternative metabolic targets beyond DNA may prove to be much more effective. PDA cells are forced to live within a particularly severe microenvironment characterized by relative hypovascularity, hypoxia, and nutrient deprivation. Thus, PDA cells must possess biochemical flexibility in order to adapt to austere conditions. A better understanding of the metabolic dependencies required by PDA to survive and thrive within a harsh metabolic milieu could reveal specific metabolic vulnerabilities. These molecular requirements can then be targeted therapeutically, and would likely be associated with a clinically significant therapeutic window since the normal tissue is so well-perfused with an abundant nutrient supply. Recent work has uncovered a number of promising therapeutic targets in the metabolic domain, and clinicians are already translating some of these discoveries to the clinic. In this review, we highlight mitochondria metabolism, non-canonical nutrient acquisition pathways (macropinocytosis and use of pancreatic stellate cell-derived alanine), and redox homeostasis as compelling therapeutic opportunities in the metabolic domain

Isospin Considerations in Correlations of Pions and BB mesons

The correlations between a $B$ meson and a pion produced nearby in phase space should respect isospin reflection symmetry $I_3 \to -I_3$. Thus, one generally expects similar $\pi^+ B^0$ and $\pi^- B^+$ correlations (non-exotic channels), and similar $\pi^- B^0$ and $\pi^+ B^+$ correlations (exotic channels). Exceptions include (a) fragmentation processes involving exchange of quarks with the producing system, (b) misidentification of charged kaons as charged pions, and (c) effects of decay products of the associated $\overline{B}$. All of these can affect the apparent signal for correlations of charged $B$ mesons with charged hadrons. The identification of the flavor of neutral $B$ mesons through the decay $B^0 \to K^{*0} J/\psi$ requires good particle identification in order that the decay $K^{*0} \to K^+ \pi^-$ not be mistaken for $\overline{K}^{*0} \to K^- \pi^+$, in which case the correlations of neutral $B$ mesons with hadrons can be underestimated.Comment: LaTeX EPSF file; 8 uuencoded figures to be submitted separatel

Noise-Adaptive Compiler Mappings for Noisy Intermediate-Scale Quantum Computers

A massive gap exists between current quantum computing (QC) prototypes, and the size and scale required for many proposed QC algorithms. Current QC implementations are prone to noise and variability which affect their reliability, and yet with less than 80 quantum bits (qubits) total, they are too resource-constrained to implement error correction. The term Noisy Intermediate-Scale Quantum (NISQ) refers to these current and near-term systems of 1000 qubits or less. Given NISQ's severe resource constraints, low reliability, and high variability in physical characteristics such as coherence time or error rates, it is of pressing importance to map computations onto them in ways that use resources efficiently and maximize the likelihood of successful runs. This paper proposes and evaluates backend compiler approaches to map and optimize high-level QC programs to execute with high reliability on NISQ systems with diverse hardware characteristics. Our techniques all start from an LLVM intermediate representation of the quantum program (such as would be generated from high-level QC languages like Scaffold) and generate QC executables runnable on the IBM Q public QC machine. We then use this framework to implement and evaluate several optimal and heuristic mapping methods. These methods vary in how they account for the availability of dynamic machine calibration data, the relative importance of various noise parameters, the different possible routing strategies, and the relative importance of compile-time scalability versus runtime success. Using real-system measurements, we show that fine grained spatial and temporal variations in hardware parameters can be exploited to obtain an average $2.9$x (and up to $18$x) improvement in program success rate over the industry standard IBM Qiskit compiler.Comment: To appear in ASPLOS'1

Visual detection of Brucella in bovine biological samples using DNA-activated gold nanoparticles

Brucellosis is a bacterial disease, which, although affecting cattle primarily, has been associated with human infections, making its detection an important challenge. The existing gold standard diagnosis relies on the culture of bacteria which is a lengthy and costly process, taking up to 45 days. New technologies based on molecular diagnosis have been proposed, either through dip-stick, immunological assays, which have limited specificity, or using nucleic acid tests, which enable to identify the pathogen, but are impractical for use in the field, where most of the reservoir cases are located. Here we demonstrate a new test based on hybridization assays with metal nanoparticles, which, upon detection of a specific pathogen-derived DNA sequence, yield a visual colour change. We characterise the components used in the assay with a range of analytical techniques and show sensitivities down to 1000 cfu/ml for the detection of Brucella. Finally, we demonstrate that the assay works in a range of bovine samples including semen, milk and urine, opening up the potential for its use in the field, in low-resource settings

An Ensemble Semi-Supervised Adaptive Resonance Theory Model with Explanation Capability for Pattern Classification

Most semi-supervised learning (SSL) models entail complex structures and iterative training processes as well as face difficulties in interpreting their predictions to users. To address these issues, this paper proposes a new interpretable SSL model using the supervised and unsupervised Adaptive Resonance Theory (ART) family of networks, which is denoted as SSL-ART. Firstly, SSL-ART adopts an unsupervised fuzzy ART network to create a number of prototype nodes using unlabeled samples. Then, it leverages a supervised fuzzy ARTMAP structure to map the established prototype nodes to the target classes using labeled samples. Specifically, a one-to-many (OtM) mapping scheme is devised to associate a prototype node with more than one class label. The main advantages of SSL-ART include the capability of: (i) performing online learning, (ii) reducing the number of redundant prototype nodes through the OtM mapping scheme and minimizing the effects of noisy samples, and (iii) providing an explanation facility for users to interpret the predicted outcomes. In addition, a weighted voting strategy is introduced to form an ensemble SSL-ART model, which is denoted as WESSL-ART. Every ensemble member, i.e., SSL-ART, assigns {\color{black}a different weight} to each class based on its performance pertaining to the corresponding class. The aim is to mitigate the effects of training data sequences on all SSL-ART members and improve the overall performance of WESSL-ART. The experimental results on eighteen benchmark data sets, three artificially generated data sets, and a real-world case study indicate the benefits of the proposed SSL-ART and WESSL-ART models for tackling pattern classification problems.Comment: 13 pages, 8 figure

Palaeomagnetic re-investigation of early permian rift basalts from the Baoshan block, SW China: Constraints on the site-of-origin of the gondwana-derived eastern cimmerian terranes

A palaeomagnetic investigation was carried out on a series of rift basalts (Woniusi Formation) that accumulated on the Baoshan block (SW China) in the Early Permian, the aim being to provide quantitative palaeogeographical information on the eastern Cimmerian terrane as it detached from eastern Gondwana. Reliable data were obtained from four locations/28 individual cooling units, and when combined with the findings of an earlier study (three locations/19 sites) indicate that breakup occurred at 41.9°S (with errors, 34.2-51.2°S). Using this information, we fit Baoshan against Gondwana within a narrow longitudinal belt close to where northeast Greater India and northwest Australia were once in close proximity. Furthermore, we suggest that Sibumasu (Simao-Burma-Malyasia-Sumatra; the largest of the eastern Cimmerian blocks) lay directly to the east, offshore of Australia; Qiangtang and Lhasa almost certainly sat to the west (off northern Greater India-SE Arabia), but we are uncertain as to their exact configuration. Our findings are compared with several rather different models that have been published in recent years. The new palaeomagnetic constraint highlights the flexibility authors currently have in reconstructing the region, principally because of the overall lack of similar high-quality data from the various blocks. We explain how new data could resolve these ambiguities, thereby offering more robust explanations for eastern Gondwana's late Palaeozoic development

Surface acoustic waves induced micropatterning of cells in gelatin methacryloyl (GelMA) hydrogels

Acoustic force patterning is an emerging technology that provides a platform to control the spatial location of cells in a rapid, accurate, yet contactless manner. However, very few studies have been reported on the usage of acoustic force patterning for the rapid arrangement of biological objects, such as cells, in a three-dimensional (3D) environment. In this study, we report on a bio-acoustic force patterning technique, which uses surface acoustic waves (SAWs) for the rapid arrangement of cells within an extracellular matrix-based hydrogel such as gelatin methacryloyl (GelMA). A proof-of-principle was achieved through both simulations and experiments based on the in-house fabricated piezoelectric SAW transducers, which enabled us to explore the effects of various parameters on the performance of the built construct. The SAWs were applied in a fashion that generated standing SAWs (SSAWs) on the substrate, the energy of which subsequently was transferred into the gel, creating a rapid, and contactless alignment of the cells (<10 s, based on the experimental conditions). Following ultraviolet radiation induced photo-crosslinking of the cell encapsulated GelMA pre-polymer solution, the patterned cardiac cells readily spread after alignment in the GelMA hydrogel and demonstrated beating activity in 5–7 days. The described acoustic force assembly method can be utilized not only to control the spatial distribution of the cells inside a 3D construct, but can also preserve the viability and functionality of the patterned cells (e.g. beating rates of cardiac cells). This platform can be potentially employed in a diverse range of applications, whether it is for tissue engineering, in vitro cell studies, or creating 3D biomimetic tissue structures