University of Ottawa

About: University of Ottawa is a education organization based out in Ottawa, Ontario, Canada. It is known for research contribution in the topics: Population & Health care. The organization has 36763 authors who have published 87034 publications receiving 2913651 citations. The organization is also known as: uOttawa & U of O.

How Generalizable Are the Results From Trials of Direct Antiviral Agents to People Coinfected With HIV/HCV in the Real World?

Abstract: (See the Editorial Commentaries by Martinello and Dore on pages 927–8.) Worldwide, approximately 5 million people are coinfected with human immunodeficiency virus (HIV) and hepatitis C (HCV) [1]. Coinfected people are heterogeneous, have complex medical needs, and are often socially disenfranchised. Injection drug use is responsible for the majority of both incident and prevalent cases in most developed countries. Despite effective HIV suppression and immune restoration, liver disease remains the leading cause of death in HIV–HCV coinfected individuals [2–4]. To reduce the clinical and healthcare burden of advanced liver disease, coinfected individuals need to be treated and cured of HCV [5–7]. Unfortunately, fewer than 10% of coinfected individuals have ever been treated [8, 9]. The development of direct-acting antivirals (DAAs) for HCV has been rightfully described as revolutionary. Based on compelling clinical trial results, multiple DAAs, including simeprevir; sofosbuvir; ledipasvir; ombitasvir; paritaprevir/ritonavir/dasabuvir (3D); and daclatasvir have been approved by licensing authorities globally [10–16]. Clinical trial results show that DAAs are well tolerated, more conveniently dosed, and highly efficacious compared with earlier interferon-based HCV therapies. Among interferon-free DAA trials, with as little as 12 to 24 weeks of treatment, sustained virologic response (SVR) rates ranged from 91% to 97% across genotypes and fibrosis stages in coinfected individuals, representing a remarkable advance compared with previous therapies [17–19]. Trials evaluating these new agents have so far included relatively small numbers of participants (subgroups ranging from 6 to 160) and have applied very strict eligibility criteria, likely excluding a substantial segment of the coinfected population. Substance abuse, comorbid medical and psychiatric conditions, advanced liver disease, and drug–drug interactions with antiretrovirals are common and among some of the primary factors that may influence access to treatment and outcomes in the real world [20, 21]. This raises the question: If a large proportion of coinfected patients are excluded from participating in clinical trials, how generalizable are DAA trials for people living with HIV–HCV coinfection?

Phosphorylation of Artemis following irradiation-induced DNA damage.

Abstract: Artemis is a DNA repair factor required for V(D)J recombination, repair of DNA damage induced by ionizing radiation (IR) or radiomimetic drugs, and the maintenance of genome integrity. During V(D)J recombination, Artemis participates in the resolution of hairpin-sealed coding ends, a step crucial to the constitution of the gene encoding for the antigen receptor of lymphocytes. The precise role of Artemis in the repair of IR-induced DNA damage remains to be elucidated. Here we show that Artemis is constitutively phosphorylated in cultured cells and undergoes additional phosphorylation events after irradiation. The IR-induced phosphorylation is mainly, although not solely, dependent on Ataxia-telangiectasia-mutated kinase (ATM). The physiological role of these phosphorylation events remains unknown, as in vitro-generated Artemis mutants, which present impaired IR-induced phosphorylation, still display an activity sufficient to complement the V(D)J recombination defect and the increased radiosensibility of Artemis-deficient cells. Thus, Artemis is an effector of DNA repair that can be phosphorylated by ATM, and possibly by DNA-PKcs and ATR depending upon the type of DNA damage.

Development of an Industrial Multi‐Injection Microreactor for Fast and Exothermic Reactions – Part II

Abstract: A Grignard reaction performed in a microreactor is presented. The reaction is of type A (highly exothermic and very rapid) and has a low yield which is attributed to a hot spot formed in the mixing zone of the reactor. The reaction yield could be significantly increased by applying the multi-injection principle, leading to better thermal control in the microreactor. Nevertheless, the microreactor plays a major role in reducing the magnitude of the hot spot. Knowing this, it was possible to design and construct an industrial microreactor with significant advantages such as modularity, high flow rate operation, and low investment expenditure (pumps and flow controller minimization).

Ytterbium can relax slowly too: a field-induced Yb2 single-molecule magnet

Abstract: An unusual dinuclear Yb2 complex isolated using a mixed ligand strategy leads to field-induced SMM behaviour. Low magnetic axiality and a large tunnelling gap lead to significant quantum tunnelling of the magnetisation, which was reduced under an applied static optimum field of 1600 Oe.

Stability Results for Steady, Spatially--Periodic Planforms

Abstract: We consider the symmetry-breaking steady state bifurcation of a spatially-uniform equilibrium solution of E(2)-equivariant PDEs. We restrict the space of solutions to those that are doubly-periodic with respect to a square or hexagonal lattice, and consider the bifurcation problem restricted to a finite-dimensional center manifold. For the square lattice we assume that the kernel of the linear operator, at the bifurcation point, consists of 4 complex Fourier modes, with wave vectors K_1=(a,b), K_2=(-b,a), K_3=(b,a), and K_4=(-a,b), where a>b>0 are integers. For the hexagonal lattice, we assume that the kernel of the linear operator consists of 6 complex Fourier modes, also parameterized by an integer pair (a,b). We derive normal forms for the bifurcation problems, which we use to compute the linear, orbital stability of those solution branches guaranteed to exist by the equivariant branching lemma. These solutions consist of rolls, squares, hexagons, a countable set of rhombs, and a countable set of planforms that are superpositions of all of the Fourier modes in the kernel. Since rolls and squares (hexagons) are common to all of the bifurcation problems posed on square (hexagonal) lattices, this framework can be used to determine their stability relative to a countable set of perturbations by varying a and b. For the hexagonal lattice, we analyze the degenerate bifurcation problem obtained by setting the coefficient of the quadratic term to zero. The unfolding of the degenerate bifurcation problem reveals a new class of secondary bifurcations on the hexagons and rhombs solution branches.