Miracle-dz/UniFAR-FTUs huggingface dataset:
Skeletal Myoblast Transplantation in Ischemic Heart Failure: Long-Term Follow-Up of the First Phase I Cohort of Patients

Background— Skeletal myoblast (SM) transplantation (Tx) in a post-myocardial infarction (MI) scar experimentally improves left ventricular (LV) ejection fraction (EF). Short-term follow-up (FU) studies have suggested that a similar benefit could clinically occur despite an increased risk of LV arrhythmias. Methods and Results— We report the long-term FU of the first worldwide cohort of grafted patients (n =9, 61.8±11.6 years, previous MI, EF ≤35%) operated on (autologous SM Tx and bypass surgery) in 2000 to 2001 and evaluated before Tx, at 1 month (M1) and at a median FU of 52 (18 to 58) months after Tx (37 patient-years). NYHA class improved from 2.5±0.5 to 1.8±0.4 at M1 (P=0.004 versus baseline) and 1.7±0.5 at FU (P=not significant versus M1; P=0.0007 versus baseline). EF increased from 24.3±4% to 31±4.1% at M1 (+28%, P=0.001 versus baseline) and remained stable thereafter (28.7±8.1%, +18% versus baseline). There were 5 hospitalizations for heart failure in 3 patients at 28.6±9.9 months, allowing implant in 2 patients with a resynchronization pacemaker. An automatic cardiac defibrillator (ACD) was implanted in 5 patients for nonsustained (n =1) or sustained (n =4) ventricular tachycardia at 12.2±18.6 (1 to 45) months. Despite a beta-blocker/amiodarone combination therapy, there were 14 appropriate shocks for 3 arrhythmic storms in 3 patients at 6, 7, and 18 months after ACD implantation. Conclusions— In this cohort of severe heart failure patients both clinical status and EF stably improve over time with a strikingly low incidence of hospitalizations for heart failure (0.13/patient-years) and the arrhythmic risk can be controlled by medical therapy and/or on-request ACD implantation.
Validation of the Stroke Prognostic Instrument-II in a Large, Modern, Community-Based Cohort of Ischemic Stroke Survivors

Background and Purpose— The risk of recurrent stroke in the modern era of secondary stroke prevention is not well defined. Several prediction models, including the Stroke Prognostic Instrument-II (SPI-II), have been created to identify patients at highest risk, but their performance in modern populations has been infrequently tested. We aimed to assess the 1-year risk of recurrence after hospital discharge in a recent, large, community-based cohort of patients with ischemic stroke and to validate the SPI-II prediction model in this cohort. Methods— From 2004 through 2006, 5575 patients with acute ischemic stroke were prospectively identified and followed for recurrent events. Kaplan-Meier statistics were used to analyze the cumulative incidence of recurrent ischemic stroke. Harrell c-statistic was calculated to determine the performance of SPI-II in predicting stroke or death at 1 year, and the log-rank test was used to compare the differences among low-, middle-, and high-risk groups. Results— Among 5575 patients with ischemic stroke, recurrence was observed in 221 during the subsequent year. Kaplan-Meier estimates of cumulative rates of recurrent stroke were 2.5%, 3.6%, and 4.8% at 3, 6, and 12 months, respectively. Rates of stroke or death for SPI-II in the low-, middle-, and high-risk groups were 8.2%, 24.5%, and 35.6%, respectively (trend, P=0.001). The c-statistic for SPI-II was 0.62 (95% CI, 0.61–0.64). Conclusions— The modern 1-year rate of recurrent stroke after hospital discharge is low but still substantial at 4.8%. SPI-II is a modestly effective tool in identifying patients with ischemic stroke at highest risk of developing recurrence or death.
Bacteria with Probiotic Capabilities Isolated from the Digestive Tract of the Ornamental Fish Pterophyllum scalare

© 2012 Monroy Dosta et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Bacteria with Probiotic Capabilities Isolated from the Digestive Tract of the Ornamental Fish Pterophyllum scalare
Triple Antihypertensive Therapy With Amlodipine, Valsartan, and Hydrochlorothiazide: A Randomized Clinical Trial

Many patients with hypertension require ≥3 agents to achieve target blood pressure (BP). The efficacy/safety of the dual combinations of valsartan (Val)/hydrochlorothiazide (HCTZ) and amlodipine (Aml)/Val in hypertension are well established. This randomized, double-blind study evaluated the efficacy/safety of triple therapy with Aml/Val/HCTZ for moderate or severe hypertension (mean sitting systolic BP: ≥145 mm Hg; mean sitting diastolic BP: ≥100 mm Hg). The study included a single-blind, placebo run-in period, followed by double-blind treatment for 8 weeks; patients were randomly assigned to 1 of 4 groups titrated to Aml/Val/HCTZ 10/320/25 mg, Val/HCTZ 320/25 mg, Aml/Val 10/320 mg, or Aml/HCTZ 10/25 mg once daily. Dual-therapy recipients received half of the target doses of both agents for the first 2 weeks, titrating to target doses during week 3. Those on triple therapy received Val/HCTZ 160.0/12.5 mg during week 1, Aml/Val/HCTZ 5.0/160.0/12.5 mg during week 2, and target doses of all 3 of the agents during week 3. Of the 4285 patients enrolled, 2271 were randomly assigned to treatment, and 2060 completed the study. Triple therapy was significantly superior to all of the dual therapies in reducing mean sitting systolic BP and mean sitting diastolic BP from baseline to end point (all P<0.0001). Significantly more patients on triple therapy achieved overall BP control (<140/90 mm Hg; P<0.0001) and systolic and diastolic control (P≤0.0002) compared with each dual therapy. Aml/Val/HCTZ was well tolerated. The benefits of triple therapy over dual therapy were observed regardless of age, sex, race, ethnicity, or baseline mean sitting systolic BP. In conclusion, this study demonstrates the efficacy/safety of treating moderate and severe hypertension with Aml/Val/HCTZ 10/320/25 mg.
ER-stress-associated functional link between Parkin and DJ-1 via a transcriptional cascade involving the tumor suppressor p53 and the spliced X-box binding protein XBP-1

Summary Parkin and DJ-1 are two multi-functional proteins linked to autosomal recessive early-onset Parkinson's disease (PD) that have been shown to functionally interact by as-yet-unknown mechanisms. We have delineated the mechanisms by which parkin controls DJ-1. Parkin modulates DJ-1 transcription and protein levels via a signaling cascade involving p53 and the endoplasmic reticulum (ER)-stress-induced active X-box-binding protein-1S (XBP-1S). Parkin triggers the transcriptional repression of p53 while p53 downregulates DJ-1 protein and mRNA expressions. We show that parkin-mediated control of DJ-1 is fully p53-dependent. Furthermore, we establish that p53 lowers the protein and mRNA levels of XBP-1S. Accordingly, we show that parkin ultimately upregulates XBP-1 levels. Subsequently, XBP-1S physically interacts with the DJ-1 promoter, thereby enhancing its promoter trans-activation, mRNA levels and protein expression. This data was corroborated by the examination of DJ-1 in both parkin- and p53-null mice brains. This transcriptional cascade is abolished by pathogenic parkin mutations and is independent of its ubiquitin-ligase activity. Our data establish a parkin-dependent ER-stress-associated modulation of DJ-1 and identifies p53 and XBP-1 as two major actors acting downstream of parkin in this signaling cascade in cells and in vivo. This work provides a mechanistic explanation for the increase in the unfolded protein response observed in PD pathology, i.e. that it is due to a defect in parkin-associated control of DJ-1.
Exendin-4 Improves Steatohepatitis by Increasing Sirt1 Expression in High-Fat Diet-Induced Obese C57BL/6J Mice

The effects of exendin-4 on Sirt1 expression as a mechanism of reducing fatty liver have not been previously reported. Therefore, we investigated whether the beneficial effects of exendin-4 treatment on fatty liver are mediated via Sirt1 in high-fat (HF) diet-induced obese C57BL/6J mice and related cell culture models. Exendin-4 treatment decreased body weight, serum free fatty acid (FA), and triglyceride levels in HF-induced obese C57BL/6J mice. Histological analysis showed that exendin-4 reversed HF-induced hepatic accumulation of lipids and inflammation. Exendin-4 treatment increased mRNA and protein expression of Sirt1 and its downstream factor, AMPK, in vivo and also induced genes associated with FA oxidation and glucose metabolism. In addition, a significant increase in the hepatic expression of Lkb1 and Nampt mRNA was observed in exendin-4-treated groups. We also observed increased expression of phospho-Foxo1 and GLUT2, which are involved in hepatic glucose metabolism. In HepG2 and Huh7 cells, mRNA and protein expressions of GLP-1R were increased by exendin-4 treatment in a dose-dependent manner. Exendin-4 enhanced protein expression of Sirt1 and phospho-AMPKα in HepG2 cells treated with 0.4 mM palmitic acid. We also found that Sirt1 was an upstream regulator of AMPK in hepatocytes. A novel finding of this study was the observation that expression of GLP-1R is proportional to exendin-4 concentration and exendin-4 could attenuate fatty liver through activation of Sirt1.
Iron Oxide Nanoparticle-Micelles (ION-Micelles) for Sensitive (Molecular) Magnetic Particle Imaging and Magnetic Resonance Imaging

Background Iron oxide nanoparticles (IONs) are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI) was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI. Methods and Results IONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles). Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS) measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem) and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles) bound to blood clots. Conclusions The presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular) MPI and warrants further investigation of the FibPep-ION-Micelle platform for in vivo, non-invasive imaging of fibrin in preclinical disease models of thrombus-related pathologies and atherosclerosis.
Identifying Complex Biological Interactions based on Categorical Gene Expression Data

A novel method, MUTIC (model utilization-based clustering), is described for identifying complex interactions between genes or gene-categories based on gene expression data. The method deals with binary categorical data, which consists of a set of gene expression profiles divided into two biologically meaningful categories. It does not require data from multiple time points. Gene expression profiles are represented by feature vectors whose component features are either gene expression values, or averaged expression values corresponding to gene ontology or protein information resource categories. A supervised learning algorithm (genetic programming) is used to learn an ensemble of classification models distinguishing the two categories based on the feature vectors corresponding to their members. Each feature is associated with a "model utilization vector," which has an entry for each high-quality classification model found, indicating whether or not the feature was used in that model. These utilization vectors are then clustered using a variant of hierarchical clustering called Omniclust. The result is a set of model-utilization-based clusters, in which features are gathered together if they are often considered together by classification models - which may be because they're co-expressed, or may be for subtler reasons involving multi-gene interactions. The MUTIC method is illustrated via applying it to a dataset regarding gene expression in human brains of various ages. Compared to traditional expression-based clustering, MUTIC yields clusters that have higher mathematical quality (in the sense of homogeneity and separation) and also yield novel insights into the underlying biological processes.
Nuclear Import of Adenovirus DNA in Vitro Involves the Nuclear Protein Import Pathway and hsc70*

Adenovirus, a respiratory virus with a double-stranded DNA genome, replicates in the nuclei of mammalian cells. We have developed a cytosol-dependent in vitro assay utilizing adenovirus nucleocapsids to examine the requirements for adenovirus docking to the nuclear pore complex and for DNA import into the nucleus. Our assay reveals that adenovirus DNA import is blocked by a competitive excess of classical protein nuclear localization sequences and other inhibitors of nuclear protein import and indicates that this process is dependent on hsc70. Previous work revealed that the hexon (coat) protein of adenovirus is the only major protein on the surface of the adenovirus nucleocapsid that docks at the nuclear pore complex. This, together with our finding that in vitro nuclear import of hexon is inhibited by an excess of classical nuclear localization sequences, suggests a role for the hexon protein in adenovirus DNA import. However, recombinant transport factors that are sufficient for hexon import in permeabilized cells do not support DNA import, indicating that there are other as yet unidentified factors required for this process.
Robustness, scalability and flexibility: Key-features in modular self-reconfigurable mobile robotics

In this paper we address some of the most important aspects in modular self-reconfigurable mobile robotics. Related work indicates that it is not sufficient to just have a flexible, scalable and robust platform but that it is necessary to preserve these capabilities in higher levels of organization to benefit from them. Hence we analyze the way in which similar platforms and the according software are implemented. Then we describe the way our own platform is implemented within the SYMBRION and REPLICATOR projects. Afterwards we show how we manage to preserve the robustness and flexibility for use by other researchers in higher levels of organization. To conclude we provide some measurements that show the general adequacy of our platform architecture to cope with the challenges posed by multi-modular self-reconfigurable robotics.
Operationalizing socially responsible investment: a non-financial fiduciary duty problem

An ever increasing body of literature is focusing on the role of the fiduciary duty principle in socially responsible investment (SRI). Typically, this body of literature emphasizes the relationship between non-financial considerations of fund managers and financial return. Generally speaking, trustees are to manage their funds in ways that best represent the financial interests of their investors. The rise of SRI however continues to give evidence that a fair share of such investors have more than purely financial interests. Consequently, even in cases where the fiduciary duty principle is not violated by way of insufficient financial returns, a non-financial fiduciary duty problem may exist. We argue that this non-financial fiduciary duty problem is aggravated by differences in the sustainability-related perceptions and priorities of SRI practitioners and beneficiaries. SRI practitioners are shown to form a relatively homogeneous epistemic community across national borders. From the perspective of ESG integration, this in turn creates an agency problem. This agency problem is mainly relevant for value-driven investors and ESG integration. Alongside the continued mainstreaming and maturing of SRI, practitioners will increasingly need to find ways to address these non-financial fiduciary responsibilities. WP No 13-002
Performance Benefits of Simultaneous Over Sequential Menus as Task Complexity Increases

To date, experimental comparisons of menu layouts have concentrated on variants of hierarchical structures of sequentially presented menus. Simultaneous menus-layouts that present multiple active menus on a screen at the same time-are an alternative arrangement that may be useful in many Web design situations. This article describes an experiment involving a between-subject comparison of simultaneous menus and their traditional sequential counterparts. A total of 20 experienced Web users used either simultaneous or sequential menus in a standard Web browser to answer questions based on U.S. Census data. Our results suggest that appropriate use of simultaneous menus can lead to improved task performance speeds without harming subjective satisfaction measures. For novice users performing simple tasks, the simplicity of sequential menus appears to be helpful, but experienced users performing complex tasks may benefit from simultaneous menus. Design improvements can amplify the benefits of simultaneous menu layouts.
Learning Sparsely Used Overcomplete Dictionaries via Alternating Minimization

We consider the problem of sparse coding, where each sample consists of a sparse linear combination of a set of dictionary atoms, and the task is to learn both the dictionary elements and the mixing coefficients. Alternating minimization is a popular heuristic for sparse coding, where the dictionary and the coefficients are estimated in alternate steps, keeping the other fixed. Typically, the coefficients are estimated via $\ell_1$ minimization, keeping the dictionary fixed, and the dictionary is estimated through least squares, keeping the coefficients fixed. In this paper, we establish local linear convergence for this variant of alternating minimization and establish that the basin of attraction for the global optimum (corresponding to the true dictionary and the coefficients) is $\order{1/s^2}$, where $s$ is the sparsity level in each sample and the dictionary satisfies RIP. Combined with the recent results of approximate dictionary estimation, this yields provable guarantees for exact recovery of both the dictionary elements and the coefficients, when the dictionary elements are incoherent.
Incidence and quality of vertigo symptoms after cochlear implantation

Abstract Objectives: To assess the incidence of vestibular disturbance in patients after cochlear implantation, and to evaluate the quality of vertigo symptoms. Study design: Prospective, observational study. Setting: Cochlear implant centre at a tertiary referral university hospital, Munich, Germany. Patients: Forty-seven adult patients undergoing unilateral cochlear implantation between 2003 and 2007. Methods: Patients were interviewed post-operatively about vertigo symptoms, using a specifically designed questionnaire. Questionnaire data were used to define patient subgroups based on probable vertigo aetiology. Cochlear implantation was performed via a retroauricular, transmastoidal approach. Thirty-six implants were Cochlear Nucleus 24 devices and 11 were MedEl devices. Results: Twenty-one (45 per cent) patients reported vertigo symptoms following cochlear implantation. The time of onset was directly post-operatively in the majority of patients. In 90 per cent, the symptoms suggested an otogenic origin. The majority of patients reported paroxysmal vertigo with a duration of seconds to minutes. Typical concomitant symptoms were tinnitus, fluctuating hearing loss and vegetative reactions. Serious disablement by vertigo was rare. Conclusion: Exposing patients to the risk of possible balance disorders associated with cochlear implantation is justified in view of the hearing rehabilitation achieved, even with today's broader indications for cochlear implantation. However, patients should in any case be informed about the possibility and quality of post-operative vertigo symptoms.
Gastric function and its contribution to the postprandial metabolic response of the Burmese python Python molurus

SUMMARY The large intact prey ingested by Burmese pythons require considerable processing by the stomach before passage into the small intestine. To investigate the function and cost of gastric digestion and its contribution to postprandial metabolic response for the Burmese python, I examined the rate of gastric digestion, the postprandial profile of gastric pH and the effects of decreasing gastric workload on the metabolic cost of digestion, referred to as specific dynamic action (SDA). Ingested meal mass (equivalent to 25% of snake body mass) was reduced by 18% within 1 day postfeeding, by which time intragastric pH had decreased from 7.5 to 2. Gastric pH was maintained at 1.5 for the next 5–7 days, after which it returned to 7.5. The SDA generated by digesting an intact rat meal was reduced by 9.1%, 26.0%, 56.5% and 66.8%, respectively, when pythons were fed steak, ground rat, liquid diet or ground rat directly infused into the small intestine. The production of HCl and enzymes and other gastric functions represent an estimated 55% of the python's SDA generated from the digestion of an intact rodent meal. Additional contributors to SDA include protein synthesis (estimated 26%), gastrointestinal upregulation (estimated 5%) and the activities of the pancreas, gallbladder, liver, kidneys and intestines during digestion (estimated 14%). Operating on a `pay before pumping' principle, pythons must expend endogenous energy in order to initiate acid production and other digestive processes before ingested nutrients can be absorbed and channeled into metabolic pathways.
IPv6 unicast and IPv4 multicast routing in OMNeT++

The deployment of IPv6 is accelerating with depletion of IPv4 address space in the last year. Audio/video streaming and overall effectiveness of multicast one-to-many data delivery are becoming popular nowadays. Interest in proper simulation and modeling has increased together with those two trends. This paper introduces two brand-new simulation modules for RIPng and PIM-DM dynamic routing protocols, which are now parts of our ANSA extension, built over the INET framework.