Alien Registration- Mcleod, Lucella (Auburn, Androscoggin County)

https://digitalmaine.com/alien_docs/30137/thumbnail.jp

Immunocytochemical localisation of proteins implicated in Ca2+ and free radical homeostasis in normal and axotomised cat spinal motoneurones: A segmental comparison with reference to amyotrophic lateral sclerosis

Motoneurones of Onufs nucleus (ON) in the sacral spinal cord enjoy relative resistance to degenerative motor conditions. It has been suggested that, in the case of amyotrophic lateral sclerosis (ALS), this resistance may relate to the differences between these motoneurones and other somatic motoneurones in the levels of Ca2+ buffering proteins ordinarily present. Ca2+ regulation and free radical homeostasis are central to the current understanding of the causes of neuronal death in ALS and therefore six proteins relevant to both of these activities were selected for further investigation in the spinal cord of the adult cat. To determine their localisation and investigate the possibility of segmental differences, immunocytochemical analyses were carried out in cervical, thoracic, lumbar, and sacral segments in the normal cat. In a second set of experiments aimed at characterising the regulation of these proteins after injury in a group of ALS-vulnerable neurones, motoneurones innervating the sartorius muscle were axotomised. Finally, post-axotomy alterations of immunoreactivity levels in Sartorius motoneurones were compared with the alterations seen after axotomy of the pudendal nerve, arising from ON. The proteins examined were calbindin (CaBP-D28k), parvalbumin (PV), calmodulin (CM), calcineurin (CaN), neuronal nitric oxide synthase (nNOS), and superoxide dismutase (SOD). Immunocytochemical labelling of perfusion fixed cat spinal cord revealed high levels of nNOS, SOD, and CaBP-D28k in ON. Full quantitative analysis showed that nNOS immunoreactivity (IR) and CaBP- D28k-IR were significantly higher in sacral motoneurones than motoneurones from cervical, thoracic, or lumbar spinal cord. Axotomised sartorius motoneurones showed significant bilateral decreases in CaBP-D28k-IR, CM-IR, and CaN-IR, and a bilateral increase in nNOS-IR. By contrast, post-axotomy alterations in ON were found to be unilateral. Furthermore, nNOS-IR in axotoniised ON was found to be decreased on the side of the lesion. The higher levels of CaBP-D28k in ON are discussed in the context of the current understanding of the functional importance of CaBP activity. It is suggested that higher levels of nNOS may relate to the possibility that pudendal motoneurones synthesise and release NO as a transmitter substance. Differential post-axotomy regulation of nNOS is hypothesised to reflect post-axotomy transmitter regulation in ON compared to a pure injury response in the sartorius motoneurones, which do not utilize NO as a transmitter. Segmental differences in the laterality of injury responses are considered in the context of segmental variations in bilateral connectivity. These findings are also discussed alongside the concept of differential vulnerability in ALS

Gravitational wave detector characterisation and transient searches

Recent gravitational wave observations have allowed for a new avenue through which to observe our universe. The detection of gravitational wave events has been possible by the advent of the advanced detector era and highly sensitive gravitational wave detectors, such as advanced LIGO and advanced Virgo. Spinning non-axisymmetric neutron stars present a promising source of gravitational waves, known as continuous waves. Such gravitational waves have yet to be detected, and are predicted to be extremely weak. In order to increase the detectors’ sensitivity to gravitational waves, they must be finely tuned to produce data without loud artefacts in either the time or frequency domains. The pursuit of identifying, characterising and removing these artefacts is knows as detector characterisation. In the first portion of this thesis, we present a range of definitions, tools, and techniques that are used in detector characterisation. I detail three case studies of work undertaken during the course of this research. These case studies draw on a broad knowledge base from staff scientists at both LIGO observatories, the detector characterisation community within the LIGO collaboration, and continuous wave search groups within the LIGO-Virgo collaborations. First, I investigate a broadening of the 60Hz noise line at the LIGO Livingston observatory during the final two observations of the initial LIGO detectors. Previous investigations by site staff linked short transients in magnetometer channels around the site with the this line broadening. I examine this suspected coupling with more scrutiny, and fail to find an instantaneous coupling between broad magnetometer glitches and the broadening of the 60Hz line. Secondly, we detail the creation of a list of known instrumental and environmental noise lines and combs in advanced LIGO’s second observation. Thirdly, we present an investigation of a comb of noise lines prevalent in the low frequencies (≤ 100Hz) of advanced LIGO’s first observing run. In collaboration with site staff, I identified the source of the comb, and the site staff took measures to reduce the contribution of the com to the strain channel. In the second portion of the thesis, we focus on data analysis methods FOR “transient” continuous waves. We examine several phenomena that can result in transient-continuous waves, and review a number of existing searches for transient-continuous waves. Then, we present a new method, reduced Bayesian blocks, built around the Bayesian blocks formalism, in order to determine whether a candidate continuous wave signal exhibits transient behaviour, and loosely constrain the beginning and ending times of any transient-continuous emission. The methods involves coarsely chunking up gravitational wave observations into several chunks of equal time. These chunks are then recompiled into all allowable blocks, where a block is a series of contiguous chunks. In each block, the evidences that the block contains signal from a given source, or only Gaussian noise, are estimated. These evidences are then used to recompile a mixed-model description of the observation. We term each arrangement of signal- and noise-blocks as “intermittencies”. By comparing the posterior probabilities of all intermittencies in a given observation, we can determine whether an observation contains a transient-continuous signal from a given source. We examine the performance of this new method, first on simple, short, simulated dataset then on a larger set of longer simulated signals. We see that the method produces results in line with our expectations. Then, we attempt to recover the injected intermittencies in the hardware injections of O2. Finally, we follow-up four outlying candidates from the first low-frequency all-sky search for continuous waves in advanced LIGO. In all four candidates, the reduced Bayesian blocks method supported the Gaussian noise model throughout the observation

Multiple species comparison of cardiac troponin T and dystrophin: unravelling the DNA behind dilated cardiomyopathy

Animals have frequently been used as models for human disorders and mutations. Following advances in genetic testing and treatment options, and the decreasing cost of these technologies in the clinic, mutations in both companion and commercial animals are now being investigated. A recent review highlighted the genes associated with both human and non-human dilated cardiomyopathy. Cardiac troponin T and dystrophin were observed to be associated with both human and turkey (troponin T) and canine (dystrophin) dilated cardiomyopathies. This review gives an overview of the work carried out in cardiac troponin T and dystrophin to date in both human and animal dilated cardiomyopathy

Mapping the Interacting Regions between Troponins T and C. Binding of TnT and TnI peptides to TnC and NMR mapping of the TnT-binding site on TnC

Muscular contraction is triggered by an increase in calcium concentration, which is transmitted to the contractile proteins by the troponin complex. The interactions among the components of the troponin complex (troponins T, C, and I) are essential to understanding the regulation of muscle contraction. While the structure of TnC is well known, and a model for the binary TnC·TnI complex has been recently published (Tung, C.-S., Wall, M. E., Gallagher, S. C., and Trewhella, J. (2000)Protein Sci. 9, 1312–1326), very little is known about TnT. Using non-denaturing gels and NMR spectroscopy, we have analyzed the interactions between TnC and five peptides from TnT as well as how three TnI peptides affect these interactions. Rabbit fast skeletal muscle peptide TnT-(160–193) binds to TnC with a dissociation constant of 30 ± 6 µm. This binding still occurs in the presence of TnI-(1–40) but is prevented by the presence of TnI-(56–115) or TnI-(96–139), both containing the primary inhibitory region of TnI. TnT-(228–260) also binds TnC. The binding site for TnT-(160–193) is located on the C-terminal domain of TnC and was mapped to the surface of TnC using NMR chemical shift mapping techniques. In the context of the model for the TnC·TnI complex, we discuss the interactions between TnT and the other troponin subunits

Tissue-specific interactions of TNI isoforms with other TN subunits and tropomyosins in C. elegans: The role of the C- and N-terminal extensions

The aim of this study is to investigate the function of the C-terminal extension of three troponin I isoforms, that are unique to the body wall muscles of Caenorhabditis elegans and to understand the molecular interactions within the TN complex between troponin I with troponin C/T, and tropomyosin. We constructed several expression vectors to generate recombinant proteins of three body wall and one pharyngeal troponin I isoforms in Escherichia coli. Protein overlay assays and Western blot analyses were performed using antibodies. We demonstrated that pharyngeal TNI-4 interacted with only the pharyngeal isoforms of troponin C/T and tropomyosin. In contrast, the body wall TNI-2 bound both the body wall and pharyngeal isoforms of these components. Similar to other invertebrates, the N-terminus of troponin I contributes to interactions with troponin C. Full-length troponin I was essential for interactions with tropomyosin isoforms. Deletion of the C-terminal extension had no direct effect on the binding of the body wall troponin I to other muscle thin filament troponin C/T and tropomyosin isoforms

First search for long-duration transient gravitational waves after glitches in the Vela and Crab pulsars

Gravitational waves (GWs) can offer a novel window into the structure and dynamics of neutron stars. Here we present the first search for long-duration quasi-monochromatic GW transients triggered by pulsar glitches. We focus on two glitches observed in radio timing of the Vela pulsar (PSR J0835-4510) on 12 December 2016 and the Crab pulsar (PSR J0534+2200) on 27 March 2017, during the Advanced LIGO second observing run (O2). We assume the GW frequency lies within a narrow band around twice the spin frequency as known from radio observatons. Using the fully-coherent transient-enabled F-statistic method to search for transients of up to four months in length. We find no credible GW candidates for either target, and through simulated signal injections we set 90% upper limits on (constant) GW strain as a function of transient duration. For the larger Vela glitch, we come close to beating an indirect upper limit for when the total energy liberated in the glitch would be emitted as GWs, thus demonstrating that similar post-glitch searches at improved detector sensitivity can soon yield physical constraints on glitch models.Comment: 10 pages, 3 figures (incl. appendices). Updated to match version accepted by PRD and fixed a few reference

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Liposarcoma: exploration of clinical prognostic factors for risk based stratification of therapy

<p>Abstract</p> <p>Background</p> <p>Prognosis and optimal treatment strategies of liposarcoma have not been fully defined. The purpose of this study is to define the distinctive clinical features of liposarcomas by assessing prognostic factors.</p> <p>Methods</p> <p>Between January 1995 and May 2008, 94 liposarcoma patients who underwent surgical resection with curative intent were reviewed.</p> <p>Results</p> <p>Fifty patients (53.2%) presented with well differentiated, 22 (23.4%) myxoid, 15 (16.0%) dedifferentiated, 5 (5.3%) round cell, and 2 (2.1%) pleomorphic histology. With the median 14 cm sized of tumor burden, about half of the cases were located in the retroperitoneum (46.8%). Seventy two (76.6%) patients remained alive with 78.1%, and 67.5% of the 5- and 10-year overall survival (OS) rates, respectively. Low grade liposarcoma (well differentiated and myxoid) had a significantly prolonged OS and disease free survival (DFS) with adjuvant radiotherapy when compared with those without adjuvant radiotherapy (5-year OS, 100% vs 66.3%, P = 0.03; 1-year DFS, 92.9% <it>vs </it>50.0%, respectively, P = 0.04). Independent prognostic factors for OS were histologic variant (P = 0.001; HR, 5.1; 95% CI, 2.0 – 12.9), and margin status (P = 0.005; HR, 4.1; 95% CI, 1.6–10.5). We identified three different risk groups: group 1 (n = 66), no adverse factors; group 2, one or two adverse factors (n = 28). The 5-year OS rate for group 1, and 2 were 91.9%, 45.5%, respectively.</p> <p>Conclusion</p> <p>The histologic subtype, and margin status were independently associated with OS, and adjuvant radiotherapy seems to confer survival benefit in low grade tumors. Our prognostic model for primary liposarcoma demonstrated distinct three groups of patients with good prognostic discrimination.</p