The omega-3 fatty acid, eicosapentaenoic acid (EPA), prevents the damaging effects of tumour necrosis factor (TNF)-alpha during murine skeletal muscle cell differentiation

Background: Eicosapentaenoic acid (EPA) is a -3 polyunsaturated fatty acid with antiinflammatory and anti-cachetic properties that may have potential benefits with regards to skeletal muscle atrophy conditions where inflammation is present. It is also reported that pathologic levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α are associated with muscle wasting, exerted through inhibition of myogenic differentiation and enhanced apoptosis. These findings led us to hypothesize that EPA may have a protective effect against skeletal muscle damage induced by the actions of TNF-α. Results: The deleterious effects of TNF-α on C2C12 myogenesis were completely inhibited by co-treatment with EPA. Thus, EPA prevented the TNF-mediated loss of MyHC expression and significantly increased myogenic fusion (p < 0.05) and myotube diameter (p < 0.05) indices back to control levels. EPA protective activity was associated with blocking cell death pathways as EPA completely attenuated TNF-mediated increases in caspase-8 activity (p < 0.05) and cellular necrosis (p < 0.05) back to their respective control levels. EPA alone significantly reduced spontaneous apoptosis and necrosis of differentiating myotubes (p < 0.001 and p < 0.05, respectively). A 2 hour pre-treatment with EPA, prior to treatment with TNF alone, gave similar results. Conclusion: In conclusion, EPA has a protective action against the damaging effects of TNF-α on C2C12 myogenesis. These findings support further investigations of EPA as a potential therapeutic agent during skeletal muscle regeneration following injury

Inductive learning spatial attention

This paper investigates the automatic induction of spatial attention from the visual observation of objects manipulated on a table top. In this work, space is represented in terms of a novel observer-object relative reference system, named Local Cardinal System, defined upon the local neighbourhood of objects on the table. We present results of applying the proposed methodology on five distinct scenarios involving the construction of spatial patterns of coloured blocks

Underuse of coronary revascularization procedures in patients considered appropriate candidates for revascularization.

Background: Ratings by an expert panel of the appropriateness of treatments may offer better guidance for clinical practice than the variable decisions of individual clinicians, yet there have been no prospective studies of clinical outcomes. We compared the clinical outcomes of patients treated medically after angiography with those of patients who underwent revascularization, within groups defined by ratings of the degree of appropriateness of revascularization in varying clinical circumstances.Methods: This was a prospective study of consecutive patients undergoing coronary angiography at three London hospitals. Before patients were recruited, a nine-member expert panel rated the appropriateness of percutaneous transluminal coronary angioplasty (PTCA) and coronary-artery bypass grafting (CABG) on a nine-point scale (with 1 denoting highly inappropriate and 9 denoting highly appropriate) for specific clinical indications. These ratings were then applied to a population of patients with coronary artery disease. However, the patients were treated without regard to the ratings. A total of 2552 patients were followed for a median of 30 months after angiography.Results: Of 908 patients with indications for which PTCA was rated appropriate (score, 7 to 9), 34 percent were treated medically; these patients were more likely to have angina at follow-up than those who underwent PTCA (odds ratio, 1.97; 95 percent confidence interval, 1.29 to 3.00). Of 1353 patients with indications for which CABG was considered appropriate, 26 percent were treated medically; they were more likely than those who underwent CABG to die or have a nonfatal myocardial infarction - the composite primary outcome (hazard ratio, 4.08; 95 percent confidence interval, 2.82 to 5.93) - and to have angina (odds ratio, 3.03; 95 percent confidence interval, 2.08 to 4.42). Furthermore, there was a graded relation between rating and outcome over the entire scale of appropriateness (P for linear trend = 0.002).Conclusions: On the basis of the ratings of the expert panel, we identified substantial underuse of coronary revascularization among patients who were considered appropriate candidates for these procedures. Underuse was associated with adverse clinical outcomes. (N Engl J Med 2001;344:645-54.) Copyright (C) 2001 Massachusetts Medical Society

A comprehensive study of infrared OH prompt emission in two comets. I. Observations and effective g-factors

We present high-dispersion infrared spectra of hydroxyl (OH) in comets C/2000 WM1 (LINEAR) and C/2004 Q2 (Machholz), acquired with the Near Infrared Echelle Spectrograph at the Keck Observatory atop Mauna Kea, Hawaii. Most of these rovibrational transitions result from photodissociative excitation of H_2O giving rise to OH "prompt" emission. We present calibrated emission efficiencies (equivalent g-factors, measured in OH photons s^(-1) [H_2O molecule]^(-1)) for more than 20 OH lines sampled in these two comets. The OH transitions analyzed cover a broad range of rotational excitation. This infrared database for OH can be used in two principal ways: (1) as an indirect tool for obtaining water production in comets simultaneously with the production of other parent volatiles, even when direct detections of H_2O are not available; and (2) as an observational constraint to models predicting the rotational distribution of rovibrationally excited OH produced by water photolysis

A Preliminary Investigation into Geopolymer Cement Mortar’s Suitability for Providing Resilient Highway Solutions

Despite local and national road authorities striving to provide motorists with a durable and safe infrastructure environment, one in six UK roads are currently classed as being in poor condition. In terms of safety, Department for Transport statistics continue to report high numbers of road fatalities; 1,780 in 2015, representing a 3% increase from the previous year. As such, research focused on developing resilient and cost effective planned/preventative highway maintenance solutions remains highly topical. Reported in this paper is research aimed at developing high performance, low impact solutions for both highway repair and skid resistance enhancement. A metakaolin/alkali silicate-based geopolymer cementitious mix design investigation is initially reported, providing key fresh and mechanical material properties such as setting time and compressive/flexural strength. Using favourable mix designs, the paper presents an assessment of geopolymer cement mortar’s suitability as a highway repair material. To this end, wear and skidding resistance characteristics of potholes repaired with geopolymer cement concrete is reported, with initial findings suggesting excellent performance levels. Finally, the paper examines the potential use of a geopolymer cement mortar-based artificial aggregate as a cost-effective alternative to calcined bauxite for high friction surfacing applications. The results of this phase of the work show potential for geopolymer application, although ongoing optimisation research is required

The Environment of M85 optical transient 2006-1: constraints on the progenitor age and mass

M85 optical transient 2006-1 (M85 OT 2006-1) is the most luminous member of the small family of V838 Mon-like objects, whose nature is still a mystery. This event took place in the Virgo cluster of galaxies and peaked at an absolute magnitude of I~-13. Here we present Hubble Space Telescope images of M85 OT 2006-1 and its environment, taken before and after the eruption, along with a spectrum of the host galaxy at the transient location. We find that the progenitor of M85 OT 2006-1 was not associated with any star forming region. The g and z-band absolute magnitudes of the progenitor were fainter than about -4 and -6 mag, respectively. Therefore, we can set a lower limit of ~50 Myr on the age of the youngest stars at the location of the progenitor that corresponds to a mass of <7 solar mass. Previously published line indices suggest that M85 has a mean stellar age of 1.6+/-0.3 Gyr. If this mean age is representative of the progenitor of M85 OT 2006-1, then we can further constrain its mass to be less than 2 solar mass. We compare the energetics and mass limit derived for the M85 OT 2006-1 progenitor with those expected from a simple model of violent stellar mergers. Combined with further modeling, these new clues may ultimately reveal the true nature of these puzzling events.Comment: 4 pages, accepted to Ap

Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases.

One major hurdle to the success of adoptive T-cell therapy is the identification of antigens that permit effective targeting of tumors in the absence of toxicities to essential organs. Previous work has demonstrated that T cells engineered to express chimeric antigen receptors (CAR-T cells) targeting the murine homolog of the colorectal cancer antigen GUCY2C treat established colorectal cancer metastases, without toxicity to the normal GUCY2C-expressing intestinal epithelium, reflecting structural compartmentalization of endogenous GUCY2C to apical membranes comprising the intestinal lumen. Here, we examined the utility of a human-specific, GUCY2C-directed single-chain variable fragment as the basis for a CAR construct targeting human GUCY2C-expressing metastases. Human GUCY2C-targeted murine CAR-T cells promoted antigen-dependent T-cell activation quantified by activation marker upregulation, cytokine production, and killing of GUCY2C-expressing, but not GUCY2C-deficient, cancer cells in vitro. GUCY2C CAR-T cells provided long-term protection against lung metastases of murine colorectal cancer cells engineered to express human GUCY2C in a syngeneic mouse model. GUCY2C murine CAR-T cells recognized and killed human colorectal cancer cells endogenously expressing GUCY2C, providing durable survival in a human xenograft model in immunodeficient mice. Thus, we have identified a human GUCY2C-specific CAR-T cell therapy approach that may be developed for the treatment of GUCY2C-expressing metastatic colorectal cancer

Comet C/2004 Q2 (MACHHOLZ): Parent Volatiles, a Search for Deuterated Methane, and Constraint on the CH4 Spin Temperature

High-dispersion (l/dl ~ 25,000) infrared spectra of Comet C/2004 Q2 (Machholz) were acquired on Nov. 28-29, 2004, and Jan. 19, 2005 (UT dates) with NIRSPEC at the Keck-2 telescope on Mauna Kea. We detected H2O, CH4, C2H2, C2H6, CO, H2CO, CH3OH, HCN, and NH3 and we conducted a sensitive search for CH3D. We report rotational temperatures, production rates, and mixing ratios (with respect to H2O) at heliocentric distances of 1.49 AU (Nov. 2004) and 1.21 AU (Jan. 2005). We highlight three principal results: (1) The mixing ratios of parent volatiles measured at 1.49 AU and 1.21 AU agree within confidence limits, consistent with homogeneous composition in the mean volatile release from the nucleus of C/2004 Q2. Notably, the relative abundance of C2H6/C2H2 is substantially higher than those measured in other comets, while the mixing ratios C2H6/H2O, CH3OH/H2O, and HCN/H2O are similar to those observed in comets, referred to as "organics-normal". (2) The spin temperature of CH4 is > 35-38 K, an estimate consistent with the more robust spin temperature found for H2O. (3) We obtained a 3s upper limit of CH3D/CH4 < 0.020 (D/H < 0.005). This limit suggests that methane released from the nucleus of C/2004 Q2 is not dominated by a component formed in extremely cold (near 10 K) environments. Formation pathways of both interstellar and nebular origin consistent with the measured D/H in methane are discussed. Evaluating the relative contributions of these pathways requires further modeling of chemistry including both gas-phase and gas-grain processes in the natal interstellar cloud and in the protoplanetary disk.Comment: Accepted by The Astrophysical Journa