New indeterminate music: The influence of the Cagean trajectory in the importance of being earmarked

This paper explores the influence of John Cage (1912-1992) on contemporary experimental music focusing on the indeterminate work The Importance of Being Earmarked (2008). Firstly through an investigation of selected works from Cage (written between the 1930s- 1960\u27s) and the concepts that form a Cagean trajectory, and secondly by showing how a contemporary composer has adopted this trajectory in the composition of a new work that combines sound-installation, theatre, and Max/MSP programming

Pencil-Beam Surveys for Faint Trans-Neptunian Objects

We have conducted pencil-beam searches for outer solar system objects to a limiting magnitude of R ~ 26. Five new trans-neptunian objects were detected in these searches. Our combined data set provides an estimate of ~90 trans-neptunian objects per square degree brighter than ~ 25.9. This estimate is a factor of 3 above the expected number of objects based on an extrapolation of previous surveys with brighter limits, and appears consistent with the hypothesis of a single power-law luminosity function for the entire trans-neptunian region. Maximum likelihood fits to all self-consistent published surveys with published efficiency functions predicts a cumulative sky density Sigma(<R) obeying log10(Sigma) = 0.76(R-23.4) objects per square degree brighter than a given magnitude R.Comment: Accepted by AJ, 18 pages, including 6 figure

Healthcare-Associated Infections in Australia: Tackling the \u27Known Unknowns\u27

Australia does not have a national healthcare-associated infection (HAI) surveillance program. Without national surveillance, we do not understand the burden of HAIs, nor can we accurately assess the effects of national infection prevention initiatives. Recent research has demonstrated disparity between existing jurisdictional-based HAI surveillance activity while also identifying broad key stakeholder support for the establishment of a national program. A uniform surveillance program will also address growing concerns about hospital performance measurements and enable public reporting of hospital data

Discovery of the Interstellar Chiral Molecule Propylene Oxide (CH3_3CHCH2_2O)

Life on Earth relies on chiral molecules, that is, species not superimposable on their mirror images. This manifests itself in the selection of a single molecular handedness, or homochirality, across the biosphere. We present the astronomical detection of a chiral molecule, propylene oxide (CH$_3$CHCH$_2$O), in absorption toward the Galactic Center. Propylene oxide is detected in the gas phase in a cold, extended molecular shell around the embedded, massive protostellar clusters in the Sagittarius B2 star-forming region. This material is representative of the earliest stage of solar system evolution in which a chiral molecule has been found

Development of analytical assays for the characterization of gene circuit enabled cell therapies

Senti Bio has built a synthetic biology platform to improve next-generation cell and gene therapies with “gene circuits.” Designing gene circuit product candidates requires the use of multicomponent genetic constructs (smart sensors, logic gates, regulator dials, multiple payloads) to reprogram cells with biological logic to sense inputs, compute decisions and respond to their cellular environments. These sophisticated, dynamic, multiple component systems require more advanced analytics to characterize insertion, expression and function of each component. For example, the SENTI-301 product candidate is a CAR-NK cell therapy for the potential treatment of hepatocellular carcinoma that contains 4 genetic components: i) a GPC3 CAR, ii) a novel IL-15, iii) a synthetic transcription factor inducible by a small molecule drug, and iv) secreted IL-12 under the control of iii. Here, we describe the development of novel assays to support this multicomponent product candidate, with focus on methods to characterize transduction (gene modification) and to demonstrate the function of these genetic modifications. Characterization of transduction relies on the ability to detect genomic modifications in the NK cells, transcription of mRNA, and translation to protein. A key challenge for multicomponent products is developing assays (DNA, RNA, and protein-based) capable of detecting each component in relation to the others within a heterogeneous cell population. Senti Bio is leveraging digital PCR (dPCR) assays to determine gene insertion and mRNA expression of multiple cellular modifications, taking advantage of improved sensitivity and precision compared to traditional qPCR assays. Multiplexed dPCR assays were developed to determine genomic copies and mRNA expression allowing us to look at the relationship of integrated DNA to mRNA expression, for each genetic component. Population analysis (transduction efficiency) of transduced NK cells is achieved by using two flow cytometry methods to detect expression of the GPC3 CAR and the synthetic transcription factor. For the CAR, a recombinant GPC3 protein was identified to detect surface expression on transduced NKs. For the synthetic transcription factor, which is only expressed intracellularly, PrimeFlow™ technology is used, which combines in situ hybridization with single cell resolution by flow cytometry. Expression of the secreted cytokines IL-15 and IL-12 are determined by ELISA. To further characterize these modifications, functional analysis is necessary to show that all components maintain their desired properties in the end product. Function of the regulated expression of IL-12 will be determined by monitoring the activation of the synthetic transcription factor after exposure to a small molecule drug (grazoprevir) by quantifying IL-12 secretion by ELISA. To show GPC3-specific killing of cancer cells, we have implemented real-time electrical impedance detection (xCELLigence) to provide real-time monitoring of killing potential and potency of the NK cells. As we advance our gene circuit technology platform, additional assays will be developed to support potency and to determine critical quality attributes and control of the manufacturing process

Contrasting alterations to synaptic and intrinsic properties in upper-cervical superficial dorsal horn neurons following acute neck muscle inflammation

Background: Acute and chronic pain in axial structures, like the back and neck, are difficult to treat, and have incidence as high as 15%. Surprisingly, most preclinical work on pain mechanisms focuses on cutaneous structures in the limbs and animal models of axial pain are not widely available. Accordingly, we developed a mouse model of acute cervical muscle inflammation and assessed the functional properties of superficial dorsal horn (SDH) neurons.&lt;p&gt;&lt;/p&gt; Results: Male C57/Bl6 mice (P24-P40) were deeply anaesthetised (urethane 2.2?g/kg i.p) and the rectus capitis major muscle (RCM) injected with 40??l of 2% carrageenan. Sham animals received vehicle injection and controls remained anaesthetised for 2?hrs. Mice in each group were sacrificed at 2?hrs for analysis. c-Fos staining was used to determine the location of activated neurons. c-Fos labelling in carrageenan-injected mice was concentrated within ipsilateral (87% and 63% of labelled neurons in C1 and C2 segments, respectively) and contralateral laminae I - II with some expression in lateral lamina V. c-Fos expression remained below detectable levels in control and sham animals. In additional experiments, whole cell recordings were obtained from visualised SDH neurons in transverse slices in the ipsilateral C1 and C2 spinal segments. Resting membrane potential and input resistance were not altered. Mean spontaneous EPSC amplitude was reduced by ~20% in neurons from carrageenan-injected mice versus control and sham animals (20.63???1.05 vs. 24.64???0.91 and 25.87???1.32 pA, respectively). The amplitude (238???33 vs. 494???96 and 593???167 pA) and inactivation time constant (12.9???1.5 vs. 22.1???3.6 and 15.3???1.4?ms) of the rapid A type potassium current (IAr), the dominant subthreshold current in SDH neurons, were reduced in carrageenan-injected mice.&lt;p&gt;&lt;/p&gt; Conclusions: Excitatory synaptic drive onto, and important intrinsic properties (i.e., IAr) within SDH neurons are reduced two hours after acute muscle inflammation. We propose this time point represents an important transition period between peripheral and central sensitisation with reduced excitatory drive providing an initial neuroprotective mechanism during the early stages of the progression towards central sensitisation