Miracle-dz/UniFAR-FTUs huggingface dataset:
Ventromedial‐frontopolar prefrontal cortex atrophy correlates with insight loss in frontotemporal dementia and Alzheimer's disease

Loss in insight is a major feature of frontotemporal dementia (FTD) but has been investigated relatively little. More importantly, the neural basis of insight loss is still poorly understood. The current study investigated insight deficit profiles across a large cohort of neurodegenerative patients (n = 81), including FTD and Alzheimer's disease (AD) patients. We employed a novel insight questionnaire, which tapped into changes across different domains: social interaction, emotion, diagnosis/treatment, language, and motivation. FTD subtypes varied considerably for insight loss, with the behavioral variant worst and the progressive non‐fluent variant least affected. All other subtypes and AD showed milder but consistent insight loss. Voxel‐based morphometry analysis revealed that overall insight loss correlated with ventromedial and frontopolar prefrontal atrophy, with exception of social interaction and emotion insight loss, which additionally correlated with lateral temporal and amygdala atrophy, respectively. Our results show that patients with neurodegenerative conditions show variable loss of insight, with ventromedial and frontopolar cortex regions appearing to be particularly important for insight. Hum Brain Mapp 35:616–626, 2014. © 2012 Wiley Periodicals, Inc.
Major injury induces increased production of interleukin-10 by cells of the immune system with a negative impact on resistance to infection.

OBJECTIVE The purpose of this study was to compare the production of interleukin-10 (IL-10) by peripheral blood mononuclear cells (PBMC) from injured patients and control subjects to determine the responsible cell types and to relate IL-10 production to the occurrence of sepsis. A mouse model of burn injury was used to confirm the human findings and to assess the importance of IL-10 in the lowered resistance to infection after injury. SUMMARY BACKGROUND DATA Severe injury is associated with depressed immune responses. Although IL-10 is known to inhibit several aspects of immune reactivity, the role of IL-10 in postinjury immune suppression remains controversial. METHODS Peripheral blood mononuclear cells from 14 burn and 12 trauma patients and 16 healthy individuals were studied at serial intervals for IL-10 production stimulated by a T-cell mitogen, phytohemagglutinin, and by bacterial lipopolysaccharide. To determine the source of IL-10, CD4+ and CD8+ lymphocyte subsets were obtained by selective depletion of PBMC with antibody-coated magnetic beads and were stimulated by anti-CD3 antibody to induce IL-10 secretion. In addition, IL-10 production by patients' PBMC in the first 10 days after injury was assessed for correlation with subsequent septic events. Anti-CD3-stimulated IL-10 production also was determined for CD4- and CD8-enriched lymphocyte subsets obtained by antibody and complement depletion of splenocytes harvested from groups of burn and sham burn mice at day 10 after injury, the time of maximal susceptibility to a septic challenge, cecal ligation and puncture (CLP). Finally, to test the importance of IL-10 in immune suppression in vivo, groups of burn and sham burn mice were treated with anti-IL-10 monoclonal antibody or control immunoglobulin G (IgG) on days 1 and 3 postinjury and were observed for survival after CLP on day 10. RESULTS Patients' PBMC produced significantly more IL-10 than did controls' PBMC 7 to 14 days after injury. Patients' CD4+ (T-helper) but not CD8+ (T-cytotoxic) lymphocytes also showed increased IL-10 production versus those of control subjects early after injury. Increased PBMC IL-10 production in the first 10 days postinjury correlated significantly (p < 0.05) with subsequent septic events. Burn mouse CD4-enriched but not CD8-enriched splenocytes produced more IL-10 than did sham burn splenocyte subsets on day 10 after injury. Burn mice treated with anti-IL-10 antibody but not with control IgG had significantly increased survival after CLP. CONCLUSION Serious injury in humans and in a mouse burn model is followed by increased stimulated production of IL-10 by cells of the immune system. The CD4+ T-helper cells appear to be a major source of IL-10 after injury. In injured patients, increased IL-10 production is correlated with subsequent septic events, and in the burn mouse, IL-10 appears to induce decreased resistance to infection.
Haemolysin produced by Vibrio mimicus activates two Cl– secretory pathways in cultured intestinal‐like Caco‐2 cells

Haemolysin (VMH) is a virulent factor produced by Vibrio mimicus, a human pathogen that causes diarrhoea. As intestinal epithelial cells are the primary targets of haemolysin, we investigated its effects on ion transport in human colonic epithelial Caco‐2 cells. VMH increased the cellular short circuit current (Isc), used to estimated ion fluxes, and 125I efflux of the cells. The VMH‐induced increases in Isc and 125I efflux were suppressed by depleting Ca2+ from the medium or by pretreating the cells with BAPTA‐AM or by Rp‐adenosin 3′,5′‐cyclic monophosphorothioate triethylammonium salt (Rp‐cAMPS). The Cl– channel inhibitors 4,4′‐disothiocyanatostibene‐2,2′‐disulfonic acid (DIDS), glybenclamide, and 5‐nitro‐2‐(3‐phenylpropylamino)benzoic acid (NPPB) suppressed the VMH‐induced increases in Isc and 125I efflux. Moreover, VMH increased the intracellular concentrations of Ca2+ and cAMP. Thus, VMH stimulates Caco‐2 cells to secrete Cl– by activating both Ca2+‐dependent and cAMP‐dependent Cl– secretion mechanisms. VMH forms ion‐permeable pores in the lipid bilayer that are non‐selectively permeable to small ions. However, the ion permeability of these pores was not inhibited by glybenclamide and DIDS, and VMH did not change the cell membrane potential. These observations indicate that the pores formed on the cell membrane by VMH are unlikely to be involved in VMH‐induced Cl– secretion. Notably, VMH stimulated fluid accumulation in the iliac loop test that was fully suppressed by a combination of DIDS and glybenclamide. Thus, Ca2+‐dependent and cAMP‐dependent Cl– secretion may be important therapeutic targets with regard to the diarrhoea that is induced by Vibrio mimicus.
Considerations for developing chronic care system for traumatic brain injury based on comparisons of cancer survivorship and diabetes management care

Abstract Experts in traumatic brain injury (TBI) rehabilitation recently proposed the framing of TBI as a chronic disease rather than a discrete event. Within the framework of the Chronic Care Model (CCM), a systematic comparison of three diseases – cancer survivorship, diabetes management and TBI chronic care – was conducted regarding chronic needs and the management of those needs. In addition, comparisons of these conditions require comparative evaluations of disease management characteristics and the survivor concept. The analysis found diabetes is more established within the CCM, where care is integrated across specialists and primary care providers. No single comparison provides a full analogue for understanding the chronic care health delivery system for TBI, indicating the need for a separate model to address needs and resources for TBI survivors. The findings from this research can provide practitioners with a context to develop a robust continued care health system for TBI. Practitioner Summary: We examine development of a chronic care system for traumatic brain injury. We conducted a systematic comparison of Chronic Care Model elements of decision and information support. Development of capabilities using a benchmark of diabetes care, with additional insights from cancer care, provides insights for implementing TBI chronic care systems.
Arthroscopic double row cuff repair with suture-bridging and autologous conditioned plasma injection: Functional and structural results

Purpose: The double row cuff repair with suture bridging is commonly used for arthroscopic rotator cuff repair (RCR). Despite its biomechanical qualities, the rate of iterative tears with this technique is important. The aim of our study was to evaluate the effect of autologous conditioned plasma (ACP) on functional results and on the rate of iterative tears after RCR by suture bridging. Materials and Methods: A consecutive series of 65 patients who underwent arthroscopic double-row suture bridge (Speed-Bridge, Arthrex) primary cuff repair of symptomatic full-thickness supraspinatus tear (retraction <3 in the Patte classification) were evaluated. Mean patient age was 60 (+/-8). The supraspinatus was repaired by knot-less bridging (SwiveLock, Arthrex) with suture tape material. 2 homogenous groups were created (A: 33 patients, B: 32 patients). In group A, all patients received, besides the cuff repair, an intra-tendinous ACP injection. Constant scores and Simple Shoulder Tests (SST) were measured pre-operatively and after a minimum follow-up period of 12 months post-operatively. Structural integrity of the repairs was evaluated by MRI according to the Sugaya classification. Sugaya >4 were considered as iterative tears. Results: Mean follow-up was 19 months (+/−42) in the 2 groups. The mean quantity of ACP injected was 6ml. (+/−1.5) and no specific complication of the injection was found. Mean preoperative Constant-Murley scores were 41,2 (±7,7) and 38 (±11)in group B. Mean normalized Constant-Murley score increased from 41 points (±7) pre-operatively to 70 points (±8) post-operatively in group A and from 38 points (±11) to 73 points (±11) in group B. There were no significative differences between the two groups (P > 0.05). In group A, 31 repairs were Sugaya 1-3 (94%), vs. 30 in group B (93%), and 1 was type 4 in group A (5%) vs. 2 in group B (8%). Conclusion: In both groups, RCR with suture bridging gave successful functional outcomes, with a low rate of iterative tear. In this preliminary study, the adjuvant effect of ACP injections could not be showed on both functional and structural results. Longer follow-up is needed to evaluate potential differences.
Impact of a landing obligation on coupled dynamics ecosystem-fishers : individual-based modelling approach applied to Eastern English Channel

L'objectif de cette these etait d'anticiper les effets de l'Obligation de Debarquement (OD) mise en place en UE depuis debut 2015 en Manche Orientale (MO). Pour accomplir ces objectifs, il a ete prevu de : i) mieux comprendre la distribution spatiale saisonniere d'especes commerciales a l'aide d'observations embarquees sur des navires commerciaux, ii) les comparer avec la distribution de l'effort de peche a fine echelle des chalutiers de fonds (OTB), et iii) developper un modele individu-centre de dynamique des flotilles, DSVM, a integrer avec le modele ecosystemique OSMOSE pour simuler l'OD. L'utilite des donnees d'observations embarquees a ete prouvee pour une majeure partie des especes echantillonnees, en utilisant une validation par la bibliographie et un indicateur geostatique. Ensuite la comparaison de l'effort de peche a fine echelle a fourni une amelioration de la quantification de l'effort de peche effectif et mis en valeur l'importance de la seiche et du rouget barbet pour la distribution des OTB en MO. De plus, l'intensite de ciblage des OTB a ete quantifiee en octobre a l'aide d'un nouvel indicateur, et demontre l'interet pour les memes especes, mais aussi la contrainte d'un faible quota de cabillaud pour les pecheurs. Les resultats du couplage OSMOSE-DSVM montrent que k'OD aurait des effets negatifs a court terme pour le revenu des pecheurs, induits par le deplacement de l'effort de peche afin d'eviter les depassements de quota, mais serait profitable a moyen terme. Cependant, l'OD provoquerait une hausse de la pression de predation produite par le cabillaud et le merlan sur les autres especes, ce qui n'ameliorerait pas l'etat global de l'ecosysteme.
Methyl dynamics for understanding hydrophobic core packing of dynamically different motifs of double‐stranded RNA binding domain of protein kinase R

Double‐stranded RNA binding domains of human protein kinase R (dsRBD‐PKR) regulate distinct cellular functions and the fate of an RNA molecule in the cell. This highly homologous domains present in multiple copies in a number of species, exhibit individual and specific functional specificity. Number of NMR and X‐ray crystallographic structural studies reveals that such domains take a common α‐β‐β‐β‐α tertiary fold. However, the functional specificities of these domains could be due to the dynamics of the individual amino acid residues, as has been shown earlier in the case of backbone dynamics of 15N‐1H of dsRNA binding motifs (dsRBMs) of human protein kinase R (PKR) (Nanduri S, Rahman F, Williams BRG, Qin J. EMBO J 2000;19:5567–5574 ). To further investigate if the differences in dynamics of the two dsRBMs are restricted to only backbone, or if the side‐chain motions are also different to the extent of influencing their packing of the two hydrophobic cores, we have investigated the methyl group dynamics using 13C‐methyl relaxation measurements. The results show that the hydrophobic core of dsRBM1 is more tightly packed than dsRBM2, and it seems to undergo less fast scale motions in the subnanosecond regime. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Effects of ingestion of bicarbonate, citrate, lactate, and chloride on sprint running.

PURPOSE Ingestion of sodium bicarbonate is known to enhance sprint performance, probably via increased buffering of intracellular acidity. The goal was to compare the effect of ingestion of sodium bicarbonate with that of other potential buffering agents (sodium citrate and sodium lactate) and of a placebo (sodium chloride) on sprinting. METHODS In a double-blind randomized crossover trial, 15 competitive male endurance runners performed a run to exhaustion 90 min after ingestion of each of the agents in the same osmolar dose relative to body mass (3.6 mosmol x kg) on separate days. The agents were packed in gelatin capsules and ingested with 750 mL of water over 90 min. During each treatment we assayed serial finger-prick blood samples for lactate and bicarbonate. A familiarization trial was used to set a treadmill speed for each runner's set of runs. We converted changes in run time between treatments into changes in a time trial of similar duration using the critical-power model, and we estimated likelihood of practical benefit using 0.5% as the smallest worthwhile change in time-trial performance. RESULTS The mean run times to exhaustion for each treatment were: bicarbonate 82.3 s, lactate 80.2 s, citrate 78.2 s, and chloride 77.4 s. Relative to bicarbonate, the effects on equivalent time-trial time were lactate 1.0%, citrate 2.2%, and chloride 2.7% (90% likely limits +/- 2.1%). Ingested lactate and citrate both appeared to be converted to bicarbonate before the run. There were no substantial differences in gut discomfort between the buffer treatments. CONCLUSION Bicarbonate is possibly more beneficial to sprint performance than lactate and probably more beneficial than citrate or chloride. We recommend ingestion of sodium bicarbonate to enhance sprint performance.
A Consumer Review-Driven Recommender Service for Web E-Commerce

Consumer reviews play an important role in various e-commerce sites like hotel reservation and app stores. Online consumer reviews are informative because they convey consumers' actual experiences and evaluations to the products and services they received. In this paper, we leverage the consumer reviews to develop a review-driven recommender service for e-commerce websites. We semantically explore the topics in reviews to derive the product features and infer the preferences of consumers for making recommendations. We conduct large-scale experiments on real-world data. The results manifest that the proposed recommender service is effective for web e-commerce.
Mechanism by Which Exosites Promote the Inhibition of Blood Coagulation Proteases by Heparin-activated Antithrombin*

Heparin activates the serpin, antithrombin, to inhibit its target blood-clotting proteases by generating new protease interaction exosites. To resolve the effects of these exosites on the initial Michaelis docking step and the subsequent acylation and conformational change steps of antithrombin-protease reactions, we compared the reactions of catalytically inactive S195A and active proteases with site-specific fluorophore-labeled antithrombins that allow monitoring of these reaction steps. Heparin bound to N,N′-dimethyl-N-(acetyl)-N′-(7-nitrobenz-3-oxa-1,3-diazol-4-yl)ethylenediamine (NBD)-fluorophore-labeled antithrombins and accelerated the reactions of the labeled inhibitor with thrombin and factor Xa similar to wild type. Equilibrium binding of NBD-labeled antithrombins to S195A proteases showed that exosites generated by conformationally activating antithrombin with a heparin pentasaccharide enhanced the affinity of the serpin for S195A factor Xa minimally 100-fold. Moreover, additional bridging exosites provided by a hexadecasaccharide heparin activator enhanced antithrombin affinity for both S195A factor Xa and thrombin at least 1000-fold. Rapid kinetic studies showed that these exosite-mediated enhancements in Michaelis complex affinity resulted from increases in kon and decreases in koff and caused antithrombin-protease reactions to become diffusion-controlled. Competitive binding and kinetic studies with exosite mutant antithrombins showed that Tyr-253 was a critical mediator of exosite interactions with S195A factor Xa; that Glu-255, Glu-237, and Arg-399 made more modest contributions to these interactions; and that exosite interactions reduced koff for the Michaelis complex interaction. Together these results show that exosites generated by heparin activation of antithrombin function both to promote the formation of an initial antithrombin-protease Michaelis complex and to favor the subsequent acylation of this complex.
Environmental issues: managing product switching intentions among Indonesian consumers

This study aims to explore the factors that make Indonesian consumers differ in their intentions to switch to products that are more eco-friendly than their current products. ,Consumers’ experiences with their current product and evaluation of its more eco-friendly alternative were simulated; the effects on intention to switch to the better product were then investigated. ,This study found that the differences in intentions to switch are attributable to loss aversion and focusing illusion. When consumers follow the principle of loss aversion (exaggeration of greater loss than gain), they are more likely to switch to leave unattractive product (i.e. a product that they perceive as contributing to environmental degradation) than when they do not. Also, when consumers experience focusing illusion concerning the environment (determining happiness based on environmental conditions), they are more likely to switch to make their lives happier than when they do not. ,In managing consumer intention to switch, companies should effectively communicate how their products save the environment. This communication could make their customers less likely to give up their current products to live happier lives. Similarly, companies could encourage target customers to switch to their products by arguing that giving up their current products would help them live happier lives. ,This study provides empirical evidence that perceived budget constraints may not inhibit consumers from switching to more eco-friendly products to live happier lives.
Being Accommodated, Well Then? ‘Scalar Narratives’ on Urban Transformation and Asylum Seekers’ Integration in Mid-Sized Cities

This article deals with the interplay between the rescaling processes of cities and pathways of asylum seekers’ integration. Building on scale theory and employing a downscaled mid-sized city in the Netherlands as a unit of analysis, two research questions are answered. Firstly, what kind of urban planning strategies do urban authorities of downscaled, midsized cities develop to rescale their cities? Secondly, how are these strategies related to the imagined pathways of asylum seeker integration? Here, the term ‘scale’ does not refer to an absolute ‘spatial object’ that is able to affect social reality. Rather, scales are socially produced through negotiation processes which are contested and heterogeneous. It is argued that Dutch urban authorities and housing corporations take a normative view of ‘pathways of integration’ and standardise these in terms of space, time and financing. By these socially produced scale processes, asylum seekers’ accommodation is well-managed, keeping the residents regulated and ‘in place’. Urban authorities utilise ‘scalar narratives’ to legitimate their interactions with asylum seekers and the way in which disadvantaged neighbourhoods in mid-sized cities are transformed. Using the Dutch mid-sized city Kerkrade as the case study, it is illustrated that local opportunity structures for integration are confined by (1) urban planning strategies mainly based on residential and tourism economies, (2) the perception of successful integration via a small-scale social mix within neighbourhoods, and (3) the neglect of public representation of cultural diversity.
Worst additive noise: An information-estimation view

The “worst additive noise” problem is considered. The problem refers to an additive channel in which the input is known to some extent. It is further assumed that the noise consists of an additive Gaussian component and an additive component of arbitrary distribution. The question is: what is the distribution over the additive noise that will minimize the mutual information between the input and the output? Two settings for this problem are considered. In the first setting a Gaussian input with a given covariance matrix is considered and it is shown that the problem can be handled in the framework of the Guo, Shamai and Verdu' I-MMSE relationship. This framework gives a simple derivation of Diggavi and Cover's result, that under a covariance constraint the “worst additive noise” distribution is Gaussian, meaning that Gaussian noise minimizes the input-output mutual information given that the input is Gaussian. The I-MMSE framework also shows that given that the input is Gaussian distributed, for any constraint on the distribution of the noise, which does not prohibit a Gaussian distribution, the “worst” distribution is a Gaussian distribution complying with the constraint. In the second setting it is assumed that the input contains a codeword from an optimal point-to-point codebook (i.e., it achieves capacity) and it is shown, for a subset of SNRs, that the minimum mutual information is obtained when the additive signal is Gaussian-like up to a given SNR.
Activation of MDA5 Requires Higher-Order RNA Structures Generated during Virus Infection

ABSTRACT Recognition of virus presence via RIG-I (retinoic acid inducible gene I) and/or MDA5 (melanoma differentiation-associated protein 5) initiates a signaling cascade that culminates in transcription of innate response genes such as those encoding the alpha/beta interferon (IFN-α/β) cytokines. It is generally assumed that MDA5 is activated by long molecules of double-stranded RNA (dsRNA) produced by annealing of complementary RNAs generated during viral infection. Here, we used an antibody to dsRNA to show that the presence of immunoreactivity in virus-infected cells does indeed correlate with the ability of RNA extracted from these cells to activate MDA5. Furthermore, RNA from cells infected with encephalomyocarditis virus or with vaccinia virus and precipitated with the anti-dsRNA antibody can bind to MDA5 and induce MDA5-dependent IFN-α/β production upon transfection into indicator cells. However, a prominent band of dsRNA apparent in cells infected with either virus does not stimulate IFN-α/β production. Instead, stimulatory activity resides in higher-order structured RNA that contains single-stranded RNA and dsRNA. These results suggest that MDA5 activation requires an RNA web rather than simply long molecules of dsRNA.