256 research outputs found
A Monopole Near a Black Hole
We study an electric charge held at rest outside a magnetically charged black
hole. We find that even if the electric charge is treated as a perturbation on
a spherically symmetric magnetic Reissner-Nordstrom hole, the geometry at large
distances is that of a magnetic Kerr-Newman black hole. When the charge
approaches the horizon and crosses it, the exterior geometry becomes that of a
Kerr-Newman hole with electric and magnetic charges and with total angular
momentum given by the standard value for a charged monopole pair. Thus, in
accordance with the "no-hair theorem", once the charge is captured by the black
hole, the angular momentum associated with the charge monopole system, looses
all traces of its exotic origin and it is perceived from the outside as common
rotation. It is argued that a similar analysis performed on Taub-NUT space
should give the same result, namely, if one holds an ordinary mass outside of
the horizon of a Taub-NUT space with only magnetic mass, the system, as seen
from large distances, is endowed with an angular momentum proportional to the
product of the two kinds of masses. When the ordinary, electric, mass reaches
the horizon, the exterior metric becomes that of a rotating Taub-NUT space.Comment: 8 pages. References adde
Individualised and complex experiences of integrative cancer support care: combining qualitative and quantitative data
Objectives: The widespread use of complementary therapies alongside biomedical treatment by people with cancer is not supported by evidence from clinical trials. We aimed to use combined qualitative and quantitative data to describe and measure individualised experiences and outcomes.
Materials and methods In three integrative cancer support centres (two breast cancer only) in the UK, consecutive patients completed the individualised outcome questionnaire Measure Yourself Concerns and Wellbeing (MYCaW) before and after treatment. MYCaW collects quantitative data (seven-point scales) and written qualitative data and the qualitative data were analysed using published categories.
Results: Seven hundred eighty-two participants, 92% female, mean age 51 years, nominated a wide range of concerns. Psychological and emotional concerns predominated. At follow-up, the mean change (improvement) in scores (nβ=β588) were: concern 1, 2.06 (95% CI 1.92β2.20); concern 2, 1.74 (95% CI 1.60β1.90); and well-being, 0.64 (95% CI 0.52β0.75). The most common responses to βwhat has been the most important aspect for you?β were βreceiving complementary therapies on an individual or group basisβ (26.2%); βsupport and understanding received from therapistsβ (17.1%) and βtime spent with other patients at the centresβ (16.1%). Positive (61.5%) and negative (38.5%) descriptions of βother things affecting your healthβ correlated with larger and smaller improvement in concerns and well-being, respectively.
Conclusions: In a multicentre evaluation, the MYCaW questionnaire provides rich data about patient experience, changes over time and perceptions of what was important to each individual with cancer within that experience. It is unlikely that meaningful evaluations of this complex intervention could be carried out by quantitative methods alone
PAM-flexible genome editing with an engineered chimeric Cas9
CRISPR enzymes require a defined protospacer adjacent motif (PAM) flanking a guide RNA-programmed target site, limiting their sequence accessibility for robust genome editing applications. In this study, we recombine the PAM-interacting domain of SpRY, a broad-targeting Cas9 possessing an NRNβ>βNYN (Rβ=βA or G, Yβ=βC or T) PAM preference, with the N-terminus of Scβ+β+, a Cas9 with simultaneously broad, efficient, and accurate NNG editing capabilities, to generate a chimeric enzyme with highly flexible PAM preference: SpRYc. We demonstrate that SpRYc leverages properties of both enzymes to specifically edit diverse PAMs and disease-related loci for potential therapeutic applications. In total, the approaches to generate SpRYc, coupled with its robust flexibility, highlight the power of integrative protein design for Cas9 engineering and motivate downstream editing applications that require precise genomic positioning
EMCCD calibration for astronomical imaging: Wide FastCam at the Telescopio Carlos SΓ‘nchez
The evident benefits of Electron Multiplying CCDs (EMCCDs) -speed, high sensitivity, low noise and their capability of detecting single photon events whilst maintaining high quantum efficiency- are bringing these kinds of detectors to many state-of-the-art astronomical instruments (Velasco et al. 2016; Oscoz et al. 2008). The EMCCDs are the perfect answer to the need for great sensitivity levels as they are not limited by the readout noise of the output amplifier, while conventional CCDs are, even when operated at high readout frame rates. Here we present a quantitative on-sky method to calibrate EMCCD detectors dedicated to astronomical imaging, developed during the commissioning process (Velasco et al. 2016) and first observations (Ricci et al. 2016, in prep.) with Wide FastCam (Marga et al. 2014) at Telescopio Carlos SΓ‘nchez (TCS) in the Observatorio del Teide
Implementation of symptom protocols for nurses providing telephone-based cancer symptom management: a comparative case study
Background: The pan-Canadian Oncology Symptom Triage and Remote Support (COSTaRS) team developed 13 evidence-informed protocols for symptom management. Aim: To build an effective and sustainable approach for implementing the COSTaRS protocols for nurses providing telephone-based symptom support to cancer patients. Methods: A comparative case study was guided by the Knowledge to Action Framework. Three cases were created for three Canadian oncology programs that have nurses providing telephone support. Teams of researchers and knowledge users: (a) assessed barriers and facilitators influencing protocol use, (b) adapted protocols for local use, (c) intervened to address barriers, (d) monitored use, and (e) assessed barriers and facilitators influencing sustained use. Analysis was within and across cases. Results: At baseline, >85% nurses rated protocols positively but barriers were identified (64-80% needed training). Patients and families identified similar barriers and thought protocols would enhance consistency among nurses teaching self-management. Twenty-two COSTaRS workshops reached 85% to 97% of targeted nurses (N = 119). Nurses felt more confident with symptom management and using the COSTaRS protocols (p < .01). Protocol adaptations addressed barriers (e.g., health records approval, creating pocket versions, distributing with telephone messages). Chart audits revealed that protocols used were documented for 11% to 47% of patient calls. Sustained use requires organizational alignment and ongoing leadership support. Linking Evidence to Action: Protocol uptake was similar to trials that have evaluated tailored interventions to improve professional practice by overcoming identified barriers. Collaborating with knowledge users facilitated interpretation of findings, aided protocol adaptation, and supported implementation. Protocol implementation in nursing requires a tailored approach. A multifaceted intervention approach increased nurses' use of evidence-informed protocols during telephone calls with patients about symptoms. Training and other interventions improved nurses' confidence with using COSTaRS protocols and their uptake was evident in some documented telephone calls. Protocols could be adapted for use by patients and nurses globally.Dawn Stacey, Esther Green, Barbara Ballantyne, Joy Tarasuk, Myriam Skrutkowski, Meg Carley, Kim Chapman, Craig Kuziemsky, Erin Kolari, Brenda Sabo, AndrΓ©anne Saucier, Tara Shaw, Lucie Tardif, Tracy Truant, Greta G. Cummings, Doris Howel
Shedding a new light on Huntington's disease: how blood can both propagate and ameliorate disease pathology
Huntington's disease (HD) is a monogenic neurodegenerative disorder resulting from a mutation in the huntingtin gene. This leads to the expression of the mutant huntingtin protein (mHTT) which provokes pathological changes in both the central nervous system (CNS) and periphery. Accumulating evidence suggests that mHTT can spread between cells of the CNS but here, we explored the possibility that mHTT could also propagate and cause pathology via the bloodstream. For this, we used a parabiosis approach to join the circulatory systems of wild-type (WT) and zQ175 mice. After surgery, we observed mHTT in the plasma and circulating blood cells of WT mice and post-mortem analyses revealed the presence of mHTT aggregates in several organs including the liver, kidney, muscle and brain. The presence of mHTT in the brain was accompanied by vascular abnormalities, such as a reduction of Collagen IV signal intensity and altered vessel diameter in the striatum, and changes in expression of Glutamic acid decarboxylase 65/67 (GAD65-67) in the cortex. Conversely, we measured reduced pathology in zQ175 mice by decreased mitochondrial impairments in peripheral organs, restored vessel diameter in the cortex and improved expression of Dopamine- and cAMP-regulated phosphoprotein 32 (DARPP32) in striatal neurons. Collectively, these results demonstrate that circulating mHTT can disseminate disease, but importantly, that healthy blood can dilute pathology. These findings have significant implications for the development of therapies in HD
Prognostic Significance of Wnt-1, Ξ²-catenin and E-cadherin Expression in Advanced Colorectal Carcinoma
Wnt/Ξ²-catenin pathway plays an important role in initiation and progression of colorectal oncogenesis. The aim of this study was to determine expression and localization of E-cadherin, Ξ²-catenin and Wnt-1 proteins in colorectal tumors. Expression of Ξ²-catenin, E-cadherin and Wnt-1 was determined by immunohistochemistry on advanced colorectal cancers. Abnormal expression of E-cadherin, Ξ²-catenin, Wnt-1 was observed. Additionally, we revealed correlations between levels of studied proteins and histoclinical data. In multivariate analysis nuclear Ξ²-catenin, higher carcinoembryonic antigen serum level before treatment, female sex and tumor localized in colon or rectum were independent unfavorable prognostic factors. These findings support the hypothesis that Wnt/Ξ²-catenin pathway plays an important role in advanced colorectal carcinoma
Two-stage hepatectomy (R0) with portal vein ligationβtowards curing patients with extended bilobular colorectal liver metastases
Potent Inhibition of HIV-1 Replication by a Tat Mutant
Herein we describe a mutant of the two-exon HIV-1 Tat protein, termed Nullbasic, that potently inhibits multiple steps of the HIV-1 replication cycle. Nullbasic was created by replacing the entire arginine-rich basic domain of wild type Tat with glycine/alanine residues. Like similarly mutated one-exon Tat mutants, Nullbasic exhibited transdominant negative effects on Tat-dependent transactivation. However, unlike previously reported mutants, we discovered that Nullbasic also strongly suppressed the expression of unspliced and singly-spliced viral mRNA, an activity likely caused by redistribution and thus functional inhibition of HIV-1 Rev. Furthermore, HIV-1 virion particles produced by cells expressing Nullbasic had severely reduced infectivity, a defect attributable to a reduced ability of the virions to undergo reverse transcription. Combination of these inhibitory effects on transactivation, Rev-dependent mRNA transport and reverse transcription meant that permissive cells constitutively expressing Nullbasic were highly resistant to a spreading infection by HIV-1. Nullbasic and its activities thus provide potential insights into the development of potent antiviral therapeutics that target multiple stages of HIV-1 infection
Deregulation of MUC4 in gastric adenocarcinoma: potential pathobiological implication in poorly differentiated non-signet ring cell type gastric cancer
MUC4 is a large, heavily glycosylated transmembrane mucin, that is implicated in the pathogenesis of various types of cancers. To date, no extensive study has been done to check the expression and functional significance of MUC4 in different types of gastric adenocarcinomas. Here, we report the expression profile of MUC4 in gastric adenocarcinomas and its function in poorly differentiated gastric non-signet ring cell carcinoma (non-SRCC) type cells. Immunohistochemical analysis using tissue microarray (TMA) showed a significant difference in MUC4 expression between normal adjacent (n=45) and gastric adenocarcinoma (n=83; P<0.001). MUC4 expression was not associated with tumour type, stage or with the degree of differentiation. To gain further insight into the significance of MUC4 expression in gastric non-SRCC cells, MUC4 was ectopically expressed in AGS, a poorly differentiated gastric non-signet ring cell line. The MUC4 overexpressing cells (AGS-MUC4) showed a significant increase (P<0.005) in cell motility and a decrease in cellular aggregation as compared with the vector-transfected cells. Furthermore, in vivo tumorigenicity analysis revealed that animals transplanted with the MUC4 overexpressing cells (AGS-MUC4) had a greater incidence of tumours (83%) in comparison to empty vector control (17%). In addition, the expression of MUC4 resulted in enhanced expression of total cellular ErbB2 and phosphorylated ErbB2. In conclusion, our results showed that MUC4 is overexpressed in gastric adenocarcinoma tissues, and that it has a role in promoting aggressive properties in poorly differentiated gastric non-SRCC cells through the activation of the ErbB2 oncoprotein
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