Lund University

About: Lund University is a education organization based out in Lund, Sweden. It is known for research contribution in the topics: Population & Cancer. The organization has 42345 authors who have published 124676 publications receiving 5016438 citations. The organization is also known as: Lunds Universitet & University of Lund.

Twelve- and 52-Week Efficacy of the Dipeptidyl Peptidase IV Inhibitor LAF237 in Metformin-Treated Patients With Type 2 Diabetes.

Abstract: OBJECTIVE —To assess the 12- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 versus placebo in patients with type 2 diabetes continuing metformin treatment RESEARCH DESIGN AND METHODS —We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 107 patients with type 2 diabetes with a 40-week extension in those completing the core study and agreeing, together with the investigator, to extend treatment to 1 year Placebo ( n = 51) or LAF237 (50 mg once daily, n = 56) was added to ongoing metformin treatment (1,500–3,000 mg/day) HbA1c and fasting plasma glucose (FPG) were measured periodically, and standardized meal tests were performed at baseline, week 12, and week 52 RESULTS —In patients randomized to LAF237, baseline HbA1c averaged 77 ± 01% and decreased at week 12 (Δ = −06 ± 01%), whereas HbA1c did not change from a baseline of 79 ± 01% in patients given placebo (between-group difference in ΔHbA1c = −07 ± 01%, P < 00001) Mean prandial glucose and FPG were significantly reduced in patients receiving LAF237 versus placebo by 22 ± 04 mmol/l ( P < 00001) and 12 ± 04 mmol/l ( P = 00057), respectively, but plasma insulin levels were not affected At end point of the extension, the between-group differences in change in mean prandial glucose, insulin, and FPG were −24 ± 06 mmol/l ( P = 00001), 40 ± 16 pmol/l ( P = 00153), and −11 ± 05 mmol/l ( P = 00312), respectively HbA1c did not change from week 12 to week 52 in LAF237-treated patients ( n = 42) but increased in participants given placebo ( n = 29) The between-group difference in ΔHbA1c after 1 year was −11 ± 02% ( P < 00001) CONCLUSIONS —Data from this study demonstrate that LAF237 effectively prevents deterioration of glycemic control when added to metformin monotherapy in type 2 diabetes

Caspase signalling controls microglia activation and neurotoxicity

Abstract: Activation of microglia and inflammation-mediated neurotoxicity are suggested to play a decisive role in the pathogenesis of several neurodegenerative disorders. Activated microglia release pro-inflammatory factors that may be neurotoxic. Here we show that the orderly activation of caspase-8 and caspase-3/7, known executioners of apoptotic cell death, regulate microglia activation through a protein kinase C (PKC)-d-dependent pathway. We find that stimulation of microglia with various inflammogens activates caspase-8 and caspase-3/7 in microglia without triggering cell death in vitro and in vivo. Knockdown or chemical inhibition of each of these caspases hindered microglia activation and consequently reduced neurotoxicity. We observe that these caspases are activated in microglia in the ventral mesencephalon of Parkinson’s disease (PD) and the frontal cortex of individuals with Alzheimer’s disease (AD). Taken together, we show that caspase-8 and caspase-3/7 are involved in regulating microglia activation. We conclude that inhibition of these caspases could be neuroprotective by targeting the microglia rather than the neurons themselves. Numerous in vivo clinical imaging and neuropathology studies suggest that activated microglia, the resident immune cells of the central nervous system, play prominent roles in the pathogenesis of neurodegenerative disorders, including PD, multiple sclerosis and AD 1,2 . Microglia are necessary for normal brain function; however, uncontrolled and over-activated microglia can trigger neurotoxicity. They are a prominent source of pro-inflammatory factors and oxidative stress such as tumour-necrosis factor (TNF)-a, nitric oxide and interleukin (IL)-1b, which are neurotoxic 2,3 . Toll-like receptors (TLRs) are a family of pattern-recognition receptors in the innate immune system. Exogenous and endogenous TLR ligands activate microglia 1 . Intracerebral delivery of lipopolysaccharide (LPS), the major component of Gram-negative bacterial walls and a ligand for TLR4, leads in vivo to microglia activation and neuronal injury, and is used as model for brain inflammation 4,5 . Synergistic effects between interferon-c (IFN-c) and several TLR ligands (including TLR4) have been suggested, suggesting crosstalk between these pro-inflammatory receptor signalling pathways 6 . Furthermore, IFN-c receptor-deficient mice are less susceptible to LPS-induced endotoxic shock than control mice 7 . Finally, TLR4 has been implicated in AD pathophysiology in several contexts. Thus, the upregulation of cytokines is TLR4 dependent in an AD mouse model 8 ; certain TLR4 single nucleotide polymorphisms are associated with increased risk for AD 9 ; the levels of TLR4 messenger RNA (mRNA) are upregulated in APP transgenic mice 10 ; and increased TLR4 expression is associated with amyloid plaque deposition in AD brain tissue 10 . Caspases, a family of cysteinyl-aspartate-specific proteases, are executioners of apoptotic cell death and their activation is considered a commitment to cell death 11,12 . Certain caspases, for example caspase-1, also play a pivotal role in immune-mediated inflammation. In this situation, caspase activation is associated with the maturation of pro-inflammatory cytokines, such as IL-1b, IL-18, IL-33, and not with apoptosis 13 . Inhibition of caspase activation protects against neuronal loss in several animal models of brain diseases involving activated microglia, including hypoxic ischaemia/stroke, acute bacterial meningitis, brain trauma and 6-hydroxydopamine and 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonism models 2,14–17 . Currently, it is unclear whether inhibition of caspase activation specifically in microglia contributes to the neuroprotective effects of caspase inhibitors. We have now discovered that microglial activation in cell and animal models of inflammation involves caspases and that inhibition of the cascade in microglia prevents neurodegeneration. Furthermore, we demonstrate that caspase activation occurs in microglia in the brains of individuals with PD and AD, and thereby we validate the observations we made in relevant cell and animal models.

An adaptive algorithm for fixation, saccade, and glissade detection in eyetracking data

Abstract: Event detection is used to classify recorded gaze points into periods of fixation, saccade, smooth pursuit, blink, and noise. Although there is an overall consensus that current algorithms for event detection have serious flaws and that a de facto standard for event detection does not exist, surprisingly little work has been done to remedy this problem. We suggest a new velocity-based algorithm that takes several of the previously known limitations into account. Most important, the new algorithm identifies so-called glissades, a wobbling movement at the end of many saccades, as a separate class of eye movements. Part of the solution involves designing an adaptive velocity threshold that makes the event detection less sensitive to variations in noise level and the algorithm settings-free for the user. We demonstrate the performance of the new algorithm on eye movements recorded during reading and scene perception and compare it with two of the most commonly used algorithms today. Results show that, unlike the currently used algorithms, fixations, saccades, and glissades are robustly identified by the new algorithm. Using this algorithm, we found that glissades occur in about half of the saccades, during both reading and scene perception, and that they have an average duration close to 24 msec. Due to the high prevalence and long durations of glissades, we argue that researchers must actively choose whether to assign the glissades to saccades or fixations; the choice affects dependent variables such as fixation and saccade duration significantly. Current algorithms do not offer this choice, and their assignments of each glissade are largely arbitrary.

Higher harmonic anisotropic flow measurements of charged particles in Pb-Pb collisions at root s(NN)=2.76 TeV

Abstract: We report on the first measurement of the triangular nu(3), quadrangular nu(4), and pentagonal nu(5) charged particle flow in Pb-Pb collisions at root s(NN) = 2.76 TeV measured with the ALICE detector at the CERN Large Hadron Collider. We show that the triangular flow can be described in terms of the initial spatial anisotropy and its fluctuations, which provides strong constraints on its origin. In the most central events, where the elliptic flow nu(2) and nu(3) have similar magnitude, a double peaked structure in the two-particle azimuthal correlations is observed, which is often interpreted as a Mach cone response to fast partons. We show that this structure can be naturally explained from the measured anisotropic flow Fourier coefficients.

Structure of the microporous titanosilicate ETS-10

Abstract: INORGANIC microporous framework solids such as zeolites are of considerable technological importance as shape-selective catalysts, ion-exchange materials and molecular sieves1. Most microporous materials known until recently were silicates, aluminosilicates1 or aluminophosphates2–4, all of which contain tetrahedrally coordinated metal atoms. In 1989, a family of microporous titanosilicates (generically denoted ETS) was discovered in which the metal atoms (Ti4+) are octahedrally coordinated5–8. A full understanding of the potential of any microporous solid to act as a molecular sieve and selective catalyst, and of the nature of the catalytic centres, requires that its structure be known. But that of the ETS materials has proved elusive because of the considerable degree of disorder that they contain. Using a combination of high-resolution electron microscopy, electron and powder X-ray diffraction, solid-state NMR, molecular modelling and chemical analysis, we have now been able to solve the structure of a prominent member of this family, ETS-10. This structure comprises corner-sharing SiO4 tetrahedra and TiO6 octahedra linked through bridging oxygen atoms. The pore system contains 12-membered rings and displays a considerable degree of disorder. Many ordered variants of ETS-10 exist, some of which are chiral.