Characterizing Triviality of the Exponent Lattice of A Polynomial through Galois and Galois-Like Groups

The problem of computing \emph{the exponent lattice} which consists of all the multiplicative relations between the roots of a univariate polynomial has drawn much attention in the field of computer algebra. As is known, almost all irreducible polynomials with integer coefficients have only trivial exponent lattices. However, the algorithms in the literature have difficulty in proving such triviality for a generic polynomial. In this paper, the relations between the Galois group (respectively, \emph{the Galois-like groups}) and the triviality of the exponent lattice of a polynomial are investigated. The \bbbq\emph{-trivial} pairs, which are at the heart of the relations between the Galois group and the triviality of the exponent lattice of a polynomial, are characterized. An effective algorithm is developed to recognize these pairs. Based on this, a new algorithm is designed to prove the triviality of the exponent lattice of a generic irreducible polynomial, which considerably improves a state-of-the-art algorithm of the same type when the polynomial degree becomes larger. In addition, the concept of the Galois-like groups of a polynomial is introduced. Some properties of the Galois-like groups are proved and, more importantly, a sufficient and necessary condition is given for a polynomial (which is not necessarily irreducible) to have trivial exponent lattice.Comment: 19 pages,2 figure

Deletion of the GABAA α2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

Rationale GABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking

C35 overexpression defines subsets of human breast cancer and its immunoreceptor tyrosine-based activation motif represents a novel treatment target

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A case of septicaemic anthrax in an intravenous drug user

<p><b>Background:</b> In 2000, Ringertz et al described the first case of systemic anthrax caused by injecting heroin contaminated with anthrax. In 2008, there were 574 drug related deaths in Scotland, of which 336 were associated with heroin and or morphine. We report a rare case of septicaemic anthrax caused by injecting heroin contaminated with anthrax in Scotland.</p> <p><b>Case Presentation:</b> A 32 year old intravenous drug user (IVDU), presented with a 12 hour history of increasing purulent discharge from a chronic sinus in his left groin. He had a tachycardia, pyrexia, leukocytosis and an elevated C-reactive protein (CRP). He was treated with Vancomycin, Clindamycin, Ciprofloxacin, Gentamicin and Metronidazole. Blood cultures grew Bacillus anthracis within 24 hours of presentation. He had a computed tomography (CT) scan and magnetic resonance imagining (MRI) of his abdomen, pelvis and thighs performed. These showed inflammatory change relating to the iliopsoas and an area of necrosis in the adductor magnus.</p> <p>He underwent an exploration of his left thigh. This revealed chronically indurated subcutaneous tissues with no evidence of a collection or necrotic muscle. Treatment with Vancomycin, Ciprofloxacin and Clindamycin continued for 14 days. Negative Pressure Wound Therapy (NPWT) device was applied utilising the Venturi™ wound sealing kit. Following 4 weeks of treatment, the wound dimensions had reduced by 77%.</p> <p><b>Conclusions:</b> Although systemic anthrax infection is rare, it should be considered when faced with severe cutaneous infection in IVDU patients. This case shows that patients with significant bacteraemia may present with no signs of haemodynamic compromise. Prompt recognition and treatment with high dose IV antimicrobial therapy increases the likelihood of survival. The use of simple wound therapy adjuncts such as NPWT can give excellent wound healing results.</p&gt

Conjugated bile acids attenuate allergen-induced airway inflammation and hyperresposiveness by inhibiting UPR transducers

© 2019 American Society for Clinical Investigation. Conjugated bile acids (CBAs), such as tauroursodeoxycholic acid (TUDCA), are known to resolve the inflammatory and unfolded protein response (UPR) in inflammatory diseases, such as asthma. Whether CBAs exert their beneficial effects on allergic airway responses via 1 arm or several arms of the UPR, or alternatively through the signaling pathways for conserved bile acid receptor, remains largely unknown. We used a house dust mite-induced (HDM-induced) murine model of asthma to evaluate and compare the effects of 5 CBAs and 1 unconjugated bile acid in attenuating allergen-induced UPR and airway responses. Expression of UPRassociated transcripts was assessed in airway brushings from human patients with asthma and healthy subjects. Here we show that CBAs, such as alanyl β-muricholic acid (AβM) and TUDCA, significantly decreased inflammatory, immune, and cytokine responses; mucus metaplasia; and airway hyperresponsiveness, as compared with other CBAs in a model of allergic airway disease. CBAs predominantly bind to activating transcription factor 6α (ATF6α) compared with the other canonical transducers of the UPR, subsequently decreasing allergen-induced UPR activation and resolving allergic airway disease, without significant activation of the bile acid receptors. TUDCA and AβM also attenuated other HDM-induced ER stress markers in the lungs of allergic mice. Quantitative mRNA analysis of airway epithelial brushings from human subjects demonstrated that several ATF6α-related transcripts were significantly upregulated in patients with asthma compared with healthy subjects. Collectively, these results demonstrate that CBA-based therapy potently inhibits the allergen-induced UPR and allergic airway disease in mice via preferential binding of the canonical transducer of the UPR, ATF6α. These results potentially suggest a novel avenue to treat allergic asthma using select CBAs

Designing a complex intervention for dementia case management in primary care

Background: Community-based support will become increasingly important for people with dementia, but currently services are fragmented and the quality of care is variable. Case management is a popular approach to care co-ordination, but evidence to date on its effectiveness in dementia has been equivocal. Case management interventions need to be designed to overcome obstacles to care co-ordination and maximise benefit. A successful case management methodology was adapted from the United States (US) version for use in English primary care, with a view to a definitive trial. Medical Research Council guidance on the development of complex interventions was implemented in the adaptation process, to capture the skill sets, person characteristics and learning needs of primary care based case managers. Methods: Co-design of the case manager role in a single NHS provider organisation, with external peer review by professionals and carers, in an iterative technology development process. Results: The generic skills and personal attributes were described for practice nurses taking up the case manager role in their workplaces, and for social workers seconded to general practice teams, together with a method of assessing their learning needs. A manual of information material for people with dementia and their family carers was also created using the US intervention as its source. Conclusions: Co-design produces rich products that have face validity and map onto the complexities of dementia and of health and care services. The feasibility of the case manager role, as described and defined by this process, needs evaluation in ‘real life’ settings

Designed Azolopyridinium Salts Block Protective Antigen Pores In Vitro and Protect Cells from Anthrax Toxin

Background:Several intracellular acting bacterial protein toxins of the AB-type, which are known to enter cells by endocytosis, are shown to produce channels. This holds true for protective antigen (PA), the binding component of the tripartite anthrax-toxin of Bacillus anthracis. Evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric PA63 binding/translocation component are related phenomena. Chloroquine and some 4-aminoquinolones, known as potent drugs against Plasmodium falciparium infection of humans, block efficiently the PA63-channel in a dose dependent way.Methodology/Principal Findings:Here we demonstrate that related positively charged heterocyclic azolopyridinium salts block the PA63-channel in the μM range, when both, inhibitor and PA63 are added to the same side of the membrane, the cis-side, which corresponds to the lumen of acidified endosomal vesicles of target cells. Noise-analysis allowed the study of the kinetics of the plug formation by the heterocycles. In vivo experiments using J774A.1 macrophages demonstrated that the inhibitors of PA63-channel function also efficiently block intoxication of the cells by the combination lethal factor and PA63 in the same concentration range as they block the channels in vitro.Conclusions/Significance:These results strongly argue in favor of a transport of lethal factor through the PA63-channel and suggest that the heterocycles used in this study could represent attractive candidates for development of novel therapeutic strategies against anthrax. © 2013 Beitzinger et al

Do Synesthetes Have a General Advantage in Visual Search and Episodic Memory? A Case for Group Studies

BACKGROUND: Some studies, most of them case-reports, suggest that synesthetes have an advantage in visual search and episodic memory tasks. The goal of this study was to examine this hypothesis in a group study. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we tested thirteen grapheme-color synesthetes and we compared their performance on a visual search task and a memory test to an age-, handedness-, education-, and gender-matched control group. The results showed no significant group differences (all relevant ps>.50). For the visual search task effect sizes indicated a small advantage for synesthetes (Cohen's d between .19 and .32). No such advantage was found for episodic memory (Cohen's d<.05). CONCLUSIONS/SIGNIFICANCE: The results indicate that synesthesia per se does not seem to lead to a strong performance advantage. Rather, the superior performance of synesthetes observed in some case-report studies may be due to individual differences, to a selection bias or to a strategic use of synesthesia as a mnemonic. In order to establish universal effects of synesthesia on cognition single-case studies must be complemented by group studies

Unmeasured improvement work: the lack of routinely collected, service-related data in NHS endoscopy units in England involved in "modernisation"

Contains fulltext : 70532.pdf (publisher's version ) (Open Access)BACKGROUND: The availability of routinely collected service-related endoscopy data from NHS endoscopy units has never been quantified. METHODS: This retrospective observational study asked 19 endoscopy units to submit copies of all in-house, service-related endoscopy data that had been routinely collected by the unit - Referral numbers, Activity, Number of patients waiting and Number of lost slots. Nine of the endoscopy units had previously participated in the Modernising Endoscopy Services (MES) project during 2003 to redesign their endoscopy services. These MES sites had access to additional funding and data collection software. The other ten (Control sites) had modernised independently. All data was requested in two phases and corresponded to eight specific time points between January 2003 and April 2006. RESULTS: Only eight of 19 endoscopy units submitted routinely collected, service-related data. Another site's data was collected specifically for the study. A further two units claimed to routinely collect service-related data but did not submit any to the study. The remaining eight did not collect any service-related endoscopy data routinely and liaised with their Trust for data. Of the eight sites submitting service-related data, only three were MES project sites. Of these three, the data variables collected were limited and none collected the complete set of endoscopy data variables requested. Of the other five sites, two collected all four endoscopy data types. Data for the three MES project sites went back as far as January 2003, whilst the five Control sites were only able to submit data from December 2003 onwards. CONCLUSION: There was a lack of service-related endoscopy data routinely collected by the study sites, especially those who had participated in the MES project. Without this data, NHS endoscopy services cannot have a true understanding of their services, cannot identify problems and cannot measure the impact of any changes. With the increasing pressures placed on NHS endoscopy services, the need to effectively inform redesign plans is paramount. We recommend the compulsory collection of service-related endoscopy data by all NHS endoscopy units using a standardised format with rigorous guidelines