A 10B-based neutron detector with stacked Multiwire Proportional Counters and macrostructured cathodes

We present the results of the measurements of the detection efficiency for a 4.7 \r{A} neutron beam incident upon a detector incorporating a stack of up to five MultiWire Proportional Counters (MWPC) with Boron-coated cathodes. The cathodes were made of Aluminum and had a surface exhibiting millimeter-deep V-shaped grooves of 45{\deg}, upon which the thin Boron film was deposited by DC magnetron sputtering. The incident neutrons interacting with the converter layer deposited on the sidewalls of the grooves have a higher capture probability, owing to the larger effective absorption film thickness. This leads to a higher overall detection efficiency for the grooved cathode when compared to a cathode with a flat surface. Both the experimental results and the predictions of the GEANT4 model suggests that a 5-counter detector stack with coated grooved cathodes has the same efficiency as a 7-counter stack with flat cathodes. The reduction in the number of counters in the stack without altering the detection efficiency will prove highly beneficial for large-area position-sensitive detectors for neutron scattering applications, for which the cost-effective manufacturing of the detector and associated readout electronics is an important objective. The proposed detector concept could be a technological option for one of the new chopper spectrometers and other instruments planned to be built at the future European Spallation Source in Sweden. These results with macrostructured cathodes generally apply not just to MWPCs but to other gaseous detectors as well.Comment: 14 pages, 9 figure

Antisense-mediated splice intervention to treat human disease: the odyssey continues

Recent approvals of oligonucleotide analogue drugs to alter gene expression have been welcomed by patient communities but not universally supported. These compounds represent a class of drugs that are designed to target a specific gene transcript, and they include a number of chemical entities to evoke different antisense mechanisms, depending upon the disease aetiology. To date, oligonucleotide therapeutics that are in the clinic or at advanced stages of translation target rare diseases, posing challenges to clinical trial design, recruitment and evaluation and requiring new evaluation paradigms. This review discusses the currently available and emerging therapeutics that alter exon selection through an effect on pre-mRNA splicing and explores emerging concerns over safety and efficacy. Although modification of synthetic nucleic acids destined for therapeutic application is common practice to protect against nuclease degradation and to influence drug function, such modifications may also confer unexpected physicochemical and biological properties. Negatively charged oligonucleotides have a strong propensity to bind extra- and intra-cellular proteins, whereas those analogues with a neutral backbone show inefficient cellular uptake but excellent safety profiles. In addition, the potential for incorporation of chemically modified nucleic acid monomers, yielded by nuclease degradation of exogenous oligonucleotides, into biomolecules has been raised and the possibility not entirely discounted. We conclude with a commentary on the ongoing efforts to develop novel antisense compounds and enhance oligonucleotide delivery in order to further improve efficacy and accelerate implementation of antisense therapeutics for human disease

Exact off-resonance near fields of small-size extended hemielliptic 2-D lenses illuminated by plane waves

The near fields of small-size extended hemielliptic lenses made of rexolite and isotropic quartz and illuminated by E- and H-polarized plane waves are studied. Variations in the focal domain size, shape, and location are presented versus the angle of incidence of the incoming wave. The problem is solved numerically in a two-dimensional formulation. The accuracy of results is guaranteed by using a highly efficient numerical algorithm based on the combination of the Muller boundary integral equations, the method of analytical regularization, and the trigonometric Galerkin discretization scheme. The analysis fully accounts for the finite size of the lens as well as its curvature and thus can be considered as a reference solution for other electromagnetic solvers. Moreover, the trusted description of the focusing ability of a finite-size hemielliptic lens can be useful in the design of antenna receivers.Comment: 7 pages, 7 figure

COVARIANCE ADJUSTMENT IN STUDIES INVOLVING OBSERVATIONAL FACTORS OR COVARIATES INFLUENCED BY TREATMENTS

We extend the definition of adjusted treatment means in the analysis of covariance to deal with the case where some of the covariates are influenced by treatments or where some of the factors are observational. In these cases, comparison of treatment means adjusted to a common value of the covariate may be inappropriate. Partially adjusted means are defined and it is shown that special cases include the usual adjusted means (adjusted to a common value for each of the covariates) and unadjusted means. In fact, in a multifactorial experiment, one can, by appropriate choice of adjustment, compare adjusted means for one factor but unadjusted means for the second factor. Partially adjusted means can be computed by any linear models software which will estimate linear combinations of the parameters

u-RANIA: a neutron detector based on \mu -RWELL technology

In the framework of the ATTRACT-uRANIA project, funded by the European Community, we are developing an innovative neutron imaging detector based on micro-Resistive WELL ($\mu$ -RWELL) technology. The $\mu$ -RWELL, based on the resistive detector concept, ensuring an efficient spark quenching mechanism, is a highly reliable device. It is composed by two main elements: a readout-PCB and a cathode. The amplification stage for this device is embedded in the readout board through a resistive layer realized by means of an industrial process with DLC (Diamond-Like Carbon). A thin layer of B$_4$C on the copper surface of the cathode allows the thermal neutrons detection through the release of $^7$Li and $\alpha$ particles in the active volume. This technology has been developed to be an efficient and convenient alternative to the $^3$He shortage. The goal of the project is to prove the feasibility of such a novel neutron detector by developing and testing small planar prototypes with readout boards suitably segmented with strip or pad read out, equipped with existing electronics or readout in current mode. Preliminary results from the test with different prototypes, showing a good agreement with the simulation, will be presented together with construction details of the prototypes and the future steps of the project.Comment: Prepared for the INSTR20 Conference Proceeding for JINS

Recovery after single-breath halothane induction of anaesthesia in daycase patients

A single-breath technique of inhalational induction of anaesthesia allows intravenous induction agents to be avoided. We have investigated recovery from anaesthesia in 40 daycase patients, using tests of psychomotor function. Patients anaesthetised with inhalational induction awaken earlier than those who receive thiopentone, but not significantly earlier. There were no significant differences in postoperative psychomotor function between patients who received thiopentone and those who had inhalational inductions. Single-breath halothane, nitrous-oxide, oxygen induction is an alternative to intravenous induction in cooperative adults, but does not confer significant benefits in terms of recovery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75757/1/j.1365-2044.1988.tb06685.x.pd

Pro-inflammatory polarization and colorectal cancer modulate alternative and intronic polyadenylation in primary human macrophages

Macrophages are essential cells of the immune system that alter their inflammatory profile depending on their microenvironment. Alternative polyadenylation in the 3'UTR (3'UTR-APA) and intronic polyadenylation (IPA) are mechanisms that modulate gene expression, in particular in cancer and activated immune cells. Yet, how polarization and colorectal cancer (CRC) cells microenvironment affect 3'UTR-APA and IPA in primary human macrophages remains unknown. Here, primary human monocytes were isolated from healthy donors, differentiated and polarized into a pro-inflammatory state and ChrRNA-Seq and 3'RNA-Seq were performed to quantify gene expression and characterize new 3’UTR-APA and IPA mRNA isoforms. Our results show that polarization of human macrophages from naïve to a pro-inflammatory state causes a marked increase both in proximal polyA site selection in the 3'UTR and in IPA events, in genes relevant for macrophage functions. Additionally, we found a negative correlation between differential gene expression and IPA during pro-inflammatory polarization of primary human macrophages. As macrophages are abundant immune cells in the CRC microenvironment that either promote or abrogate cancer progression, we investigated how indirect exposure to CRC cells affects macrophage gene expression and 3'UTR-APA and IPA mRNA events. Co-culture with CRC cells alters the inflammatory phenotype of macrophages, increases the expression of pro tumoral genes and induce 3’UTR-APA alterations. Notably, some of these gene expression differences were also found in tumour-associated macrophages of CRC patients, indicating that they are physiological relevant. Upon macrophage pro inflammatory polarization SRSF12 is the pre-mRNA processing gene that is most upregulated. After SRSF12 knockdown in M1 macrophages there is a global downregulation of gene expression, in particular in genes involved in gene expression regulation and in immune responses. Our results reveal new 48 3’UTR-APA and IPA mRNA isoforms produced during pro-inflammatory polarization of primary human macrophages and CRC co-culture that may be used in the future as diagnostic or therapeutic tools