Miracle-dz/UniFAR-FTUs huggingface dataset:
Active Transport of the Ubiquitin Ligase MID1 along the Microtubules Is Regulated by Protein Phosphatase 2A

Mutations in the MID1 protein have been found in patients with Opitz BBB/G syndrome (OS), which is characterised by multiple malformations of the ventral midline. MID1 is a microtubule-associated protein that stabilizes microtubules and, in association with the regulatory subunit of protein phosphatase 2A (PP2A), α4, provides ubiquitin ligase activity for the ubiquitin-specific modification of PP2A. Using Fluorescence Recovery After Photobleaching (FRAP) technology, we show here that MID1 is actively and bi-directionally transported along the microtubules, and that this movement is directly linked to its MAP kinase and PP2A-mediated phosphorylation status. Intact transport depends on both kinesins and dyneins and is inhibited upon colcemide treatments. MID1 proteins carrying missense mutations in the α4 binding domain still bind the microtubules but cannot be actively transported. Likewise, knock-down of the α4 protein, inhibition of PP2A activity by okadaic acid and fostriecin or the simulation of permanent phosphorylation at Ser96 in MID1 stop the migration of MID1-GFP, while preserving its microtubule-association. In summary, our data uncover an unexpected and novel function for PP2A, its regulatory subunit α4 and PP2A/α4/mTOR signaling in the active transport of the MID1 ubiquitin ligase complex along the cytoskeleton. Furthermore, a failure in the microtubule directed transport of this protein complex would be an attractive mechanism underlying the pathogenesis of OS in patients with B-box1 mutations.
Time course and pattern of optic fiber regeneration following tectal lobe removal in the goldfish

Following single tectal lobe removal in the adult goldfish, Carassius auratus, the pattern of regeneration of the optic fibers which had previously projected to that tectum was examined at 1, 2, 4, 6, 8, 10, and 12 weeks postoperative using 3H‐proline radioautography. We found that regenerating optic fibers grew across the midline through the transverse, minor, horizontal, and posterior commissures to innervate the remaining tectum. At early postoperative times innervation of the tectum was continuous, while later, the regenerating fibers segregated into discrete patches in the superficial layers of the tectum. In addition, regenerating fibers also grew into non‐optic centers/pathways such as the habenula, the fasciculus retroflexus, the forebrain, the torus semicircularis, the valvula and corpus cerebelli, the hypothalamus, and the medulla. While optic fibers were no longer apparent in the habenula and the fasciculus retroflexus after 2 weeks postoperative, all other structures were still occupied by the fibers at 12 weeks postoperative. Since most of the innervated pathways were either tectal efferent pathways, which should contain degenerating debris and proliferating glial cells after the tectal removal, or pathways closely associated with traumatized areas, we suggest that degenerating axonal debris and proliferating glia may play an important role in guiding regenerating fibers in this system.
Evaluating Amyloid-beta Oligomers in Cerebrospinal Fluid as a Biomarker for Alzheimer's Disease

The current study evaluated amyloid-b oligomers (Abo) in cerebrospinal fluid as a clinical biomarker for Alzheimer’s disease (AD). We developed a highly sensitive Abo ELISA using the same N-terminal monoclonal antibody (82E1) for capture and detection. CSF samples from patients with AD, mild cognitive impairment (MCI), and healthy controls were examined. The assay was specific for oligomerized Ab with a lower limit of quantification of 200 fg/ml, and the assay signal showed a tight correlation with synthetic Abo levels. Three clinical materials of well characterized AD patients (n = 199) and cognitively healthy controls (n = 148) from different clinical centers were included, together with a clinical material of patients with MCI (n = 165). Abo levels were elevated in the all three AD-control comparisons although with a large overlap and a separation from controls that was far from complete. Patients with MCI who later converted to AD had increased Abo levels on a group level but several samples had undetectable levels. These results indicate that presence of high or measurable Abo levels in CSF is clearly associated with AD, but the overlap is too large for the test to have any diagnostic potential on its own. Citation: Hölttä M, Hansson O, Andreasson U, Hertze J, Minthon L, et al. (2013) Evaluating Amyloid-b Oligomers in Cerebrospinal Fluid as a Biomarker for Alzheimer’s Disease. PLoS ONE 8(6): e66381. doi:10.1371/journal.pone. 0066381 Editor: Sergio T. Ferreira, Federal University of Rio de Janeiro, Brazil Received December 18, 2012; Accepted May 4, 2013; Published June 14, 2013 Copyright: 2013 Hölttä et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by Stiftelsen Gamla tjänarinnor, Gun och Bertil Stohnes stiftelse, Demensfonden, Kungliga och Hvitfeldtska stiftelsen, Stiftelsen Greta Johansson och Brita Anderssons Minnesfond, Adlerbertska stiftelsen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: mikko.holtta@neuro.gu. se
Impact of Appropriate Antimicrobial Therapy for Patients with Severe Sepsis and Septic Shock – A Quality Improvement Study

Background There is ample literature available on the association between both time to antibiotics and appropriateness of antibiotics and clinical outcomes from sepsis. In fact, the current state of debate surrounds the balance to be struck between prompt empirical therapy and care in the choice of appropriate antibiotics (both in terms of the susceptibility of infecting organism and minimizing resistance arising from use of broad-spectrum agents). The objective of this study is to determine sepsis bundle compliance and the appropriateness of antimicrobial therapy in patients with severe sepsis and septic shock and its impact on outcomes. Material This study was conducted in the ICU of a tertiary care, private hospital in São Paulo, Brazil. A retrospective cohort study was conducted from July 2005 to December 2012 in patients with severe sepsis and septic shock. Results A total of 1,279 patients were identified with severe sepsis and septic shock, of which 358 (32.1%) had bloodstream infection (BSI). The inpatient mortality rate was 29%. In evaluation of the sepsis bundle, over time there was a progressive increase in serum arterial lactate collection, obtaining blood cultures prior to antibiotic administration, administration of broad-spectrum antibiotics within 1 hour, and administration of appropriate antimicrobials, with statistically significant differences in the later years of the study. We also observed a significant decrease in mortality. In patients with bloodstream infection, after adjustment for other covariates the administration of appropriate antimicrobial therapy was associated with a decrease in mortality in patients with severe sepsis and septic shock (p = 0.023). Conclusions The administration of appropriate antimicrobial therapy was independently associated with a decline in mortality in patients with severe sepsis and septic shock due to bloodstream infection. As protocol adherence increased over time, the crude mortality rate decreased, which reinforces the need to implement institutional guidelines and monitor appropriate antimicrobial therapy compliance.
Using Ecological Niche Models and Niche Analyses to Understand Speciation Patterns: The Case of Sister Neotropical Orchid Bees

The role of past connections between the two major South American forested biomes on current species distribution has been recognized a long time ago. Climatic oscillations that further separated these biomes have promoted parapatric speciation, in which many species had their continuous distribution split, giving rise to different but related species (i.e., different potential distributions and realized niche features). The distribution of many sister species of orchid bees follow this pattern. Here, using ecological niche models and niche analyses, we (1) tested the role of ecological niche differentiation on the divergence between sister orchid-bees (genera Eulaema and Eufriesea) from the Amazon and Atlantic forests, and (2) highlighted interesting areas for new surveys. Amazonian species occupied different realized niches than their Atlantic sister species. Conversely, species of sympatric but distantly related Eulaema bees occupied similar realized niches. Amazonian species had a wide potential distribution in South America, whereas Atlantic Forest species were more limited to the eastern coast of the continent. Additionally, we identified several areas in need of future surveys. Our results show that the realized niche of Atlantic-Amazonian sister species of orchid bees, which have been previously treated as allopatric populations of three species, had limited niche overlap and similarity. These findings agree with their current taxonomy, which treats each of those populations as distinct valid species.
Molecular cloning, sequence analysis, and expression of the yeast alcohol acetyltransferase gene

The ATF1 gene, which encodes alcohol acetyltransferase (AATase), was cloned from Saccharomyces cerevisiae and brewery lager yeast (Saccharomyces uvarum). The nucleotide sequence of the ATF1 gene isolated from S. cerevisiae was determined. The structural gene consists of a 1,575-bp open reading frame that encodes 525 amino acids with a calculated molecular weight of 61,059. Although the yeast AATase is considered a membrane-bound enzyme, the results of a hydrophobicity analysis suggested that this gene product does not have a membrane-spanning region that is significantly hydrophobic. A Southern analysis of the yeast genomes in which the ATF1 gene was used as a probe revealed that S. cerevisiae has one ATF1 gene, while brewery lager yeast has one ATF1 gene and another, homologous gene (Lg-ATF1). Transformants carrying multiple copies of the ATF1 gene or the Lg-ATF1 gene exhibited high AATase activity in static cultures and produced greater concentrations of acetate esters than the control.
Generative Feature Language Models for Mining Implicit Features from Customer Reviews

Online customer reviews are very useful for both helping consumers make buying decisions on products or services and providing business intelligence. However, it is a challenge for people to manually digest all the opinions buried in large amounts of review data, raising the need for automatic opinion summarization and analysis. One fundamental challenge in automatic opinion summarization and analysis is to mine implicit features, i.e., recognizing the features implicitly mentioned (referred to) in a review sentence. Existing approaches require many ad hoc manual parameter tuning, and are thus hard to optimize or generalize; their evaluation has only been done with Chinese review data. In this paper, we propose a new approach based on generative feature language models that can mine the implicit features more effectively through unsupervised statistical learning. The parameters are optimized automatically using an Expectation-Maximization algorithm. We also created eight new data sets to facilitate evaluation of this task in English. Experimental results show that our proposed approach is very effective for assigning features to sentences that do not explicitly mention the features, and outperforms the existing algorithms by a large margin.
The effects of neuromuscular taping on gait walking strategy in a patient with joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type

Objective: In this case study, biomechanical alterations induced by neuromuscular taping (NMT) were quantified, during walking, in a patient with joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type (JHS/EDS-HT). Methods: A female JHS/EDS-HT patient underwent NMT applications over the low back spine and bilaterally to the knee. Quantitative gait analyses were collected before the NMT application and at the end of the treatment (2 weeks after the first application of NMT). Results: At the end of treatment following the NMT application, left step length showed improvements in cadence and velocity, the left knee showed a reduction in its flexed position at initial contact, and the right ankle joint improved its position at initial contact and in the swing phase. Improvements were also found in kinetics, in terms of the ankle moment and power. Conclusions: Results show that NMT seems to be a promising low-cost intervention for improving gait strategy in patients with JHS/EDS-HT. Further investigations are needed to assess the effects of this treatment intervention on pathological symptoms.
Self-Management Strategies for Stress and Anxiety Used by Nontreatment Seeking Veteran Primary Care Patients.

INTRODUCTION One of the most common reasons individuals do not seek mental health treatment is a preference to manage emotional concerns on their own. Self-management refers to the strategies that individuals use on their own (i.e., without professional guidance) to manage symptoms. Little research has examined self-management for anxiety despite its potential utility as the first step in a stepped care approach to primary care. The objectives of this study were to describe patients' anxiety self-management strategies, identify which types were perceived to be effective, and explore potential correlates. MATERIALS AND METHODS This was an exploratory descriptive study (N = 182) of nontreatment seeking Veterans Health Administration primary care patients (M = 58.3 years of age, SD = 14.9) who reported current anxiety symptoms (≥8 on Generalized Anxiety Disorder-7). The Institutional Review Board approved the study, and all participants provided informed consent. We assessed self-management strategies, anxiety and depression symptoms, and past-year treatment via telephone. Two independent raters coded strategies into 1 of 7 categories (kappa = 0.85) and 23 subcategories (kappa M = 0.82, SD = 0.16). RESULTS Participants reported nearly universal (98%) use of self-management, with an average of 2.96 (SD = 1.2) strategies used in the past 3 months, and 91% of all strategies perceived as effective. Self-care (37.0%), cognitive (15.8%), and avoidance (15.1%) strategies were reported most commonly; the most prevalent subcategories were exercise (11.0% of all strategies), redirecting thoughts (9.1%), and family/friends (8.1%). Age and depression screen status were associated with self-management strategy use. CONCLUSION Our results demonstrate the ubiquity and high perceived effectiveness of self-management for anxiety among Veteran primary care patients. Although avoidance strategies were fairly common, self-care strategies, particularly exercising, and cognitive strategies, such as redirecting thoughts, were most prevalent in this sample. Strengths of the study include its novelty, our sample of non-treatment seeking Veteran primary care patients with current symptoms, and the open-ended format of the strategies questions. Limitations include reliance on self-report data, dichotomous response options for the perceived effectiveness item, limited number of potential correlates, and sampling from a single medical center. Overall, this research highlights the opportunity that health care providers have to engage primary care patients around self-management to determine what strategies they are using and how effective those strategies may be. Future directions include identification of the most effective and feasible self-management strategies for anxiety to facilitate promotion of evidence-based self-management among primary care patients.
Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts.

Recently, development of a caveolin-1-deficient (Cav-1 null) mouse model has allowed the detailed analysis of caveolin-1's function in the context of a whole animal. Interestingly, we now report that the hearts of Cav-1 null mice are markedly abnormal, despite the fact that caveolin-1 is not expressed in cardiac myocytes. However, caveolin-1 is abundantly expressed in the nonmyocytic cells of the heart, i.e., cardiac fibroblasts and endothelia. Quantitative imaging studies of Cav-1 null hearts demonstrate a significantly enlarged right ventricular cavity and a thickened left ventricular wall with decreased systolic function. Histological analysis reveals myocyte hypertrophy with interstitial/perivascular fibrosis. Because caveolin-1 is thought to act as a negative regulator of the p42/44 MAP kinase cascade, we performed Western blot analysis with phospho-specific antibodies that only recognize activated ERK1/2. As predicted, the p42/44 MAP kinase cascade is hyperactivated in Cav-1 null heart tissue (i.e., interstitial fibrotic lesions) and isolated cardiac fibroblasts. In addition, endothelial and inducible nitric oxide synthase levels are dramatically upregulated. Thus loss of caveolin-1 expression drives p42/44 MAP kinase activation and cardiac hypertrophy.
Nitric Oxide Functions as a Positive Regulator of Root Hair Development

The root epidermis is composed by two cell types: trichoblasts (or hair cells) and atrichoblasts (or non-hair cells). In lettuce (Lactuca sativa cv. Grand Rapids var. Rapidmor oscura) plants grown hydroponically in water, the root epidermis did not form root hairs. The addition of 10 µM sodium nitroprusside (SNP), a nitric oxide (NO) donor, resulted in almost all rhizodermal cells differentiated into root hairs. Treatment with the synthetic auxin 1-naphthyl acetic acid (NAA) displayed a significant increase of root hair formation (RHF) that was prevented by the specific NO scavenger carboxy-PTIO (cPTIO). In Arabidopsis, two mutants have been shown to be defective in NO production and to display altered phenotypes in which NO is implicated. Arabidopsis nos1 has a mutation in an NO synthase structural gene (NOS1), and the nia1 nia2 double mutant is null for nitrate reductase (NR) activity. We observed that both mutants were affected in their capacity of developing root hairs. Root hair elongation was significantly reduced in nos1 and nia1 nia2 mutants as well as in cPTIO-treated wild type plants. A correlation was found between endogenous NO level in roots detected by the fluorescent probe DAF-FM DA and RHF. In Arabidopsis, as well as in lettuce, cPTIO blocked the NAA-induced root hair elongation. Taken together, these results indicate that: (i) NO is a critical molecule in the process leading to RHF, and (ii) NO is involved in the auxin-signaling cascade leading to RHF.
IMM-JVC and IMM-JPDA for closely maneuvering targets

Efficient and reliable multiple target tracking methods require the use of sophisticated data association as well as positional estimation algorithms. Two different approaches can be employed in the development of an assignment strategy for data association. This paper presents a comparative study of two assignment alternatives, namely the JVC (unique association of a measurement to an existing track) and JPDA (nonunique association of a measurement to an existing track) algorithms. The above assignment strategies are then both combined with an interacting multiple model (IMM) positional estimator, and the respective tracking performance of the IMM-JVC and IMM-JPDA algorithms is evaluated using two critical scenarios involving a pair of closely maneuvering targets. An analysis of the simulation results is carried out, permitting for a comparison of the JVC and JPDA association algorithms, which ultimately demonstrates the superiority of the IMM-JVC algorithm.
Fair rate allocation, routing, and stream control scheduling in MIMO-based WMNs

Multiple-Input Multiple-Output (MIMO) technology has great potential for improving the throughput of Wireless mesh networks (WMNs). In this paper, we investigate joint rate allocation, routing, and stream control scheduling problem in MIMO-based WMNs, where multiple antennas are exploited to increase the capacity via interference suppression (IS) and/or spatial multiplexing (SM). The notion of transmission configuration (TC) is considered and a heuristic algorithm is proposed to find a good subset of all possible TCs. Using these TCs, we present convex programming (CP) formulations to find a proportional fair rate allocation solution. The simulation results demonstrate that performance of the proposed heuristic algorithm is very near to the optimal solution. The computational complexity of the proposed heuristic algorithm is substantially less compared to the optimal solution.
A Bias and Variance Analysis for Multistep-Ahead Time Series Forecasting

Multistep-ahead forecasts can either be produced recursively by iterating a one-step-ahead time series model or directly by estimating a separate model for each forecast horizon. In addition, there are other strategies; some of them combine aspects of both aforementioned concepts. In this paper, we present a comprehensive investigation into the bias and variance behavior of multistep-ahead forecasting strategies. We provide a detailed review of the different multistep-ahead strategies. Subsequently, we perform a theoretical study that derives the bias and variance for a number of forecasting strategies. Finally, we conduct a Monte Carlo experimental study that compares and evaluates the bias and variance performance of the different strategies. From the theoretical and the simulation studies, we analyze the effect of different factors, such as the forecast horizon and the time series length, on the bias and variance components, and on the different multistep-ahead strategies. Several lessons are learned, and recommendations are given concerning the advantages, disadvantages, and best conditions of use of each strategy.
A Hybrid Lossless-Lossy Binary Image Compression Scheme

In this paper, the authors present a binary image compression scheme that can be used either for lossless or lossy compression requirements. This scheme contains five new contributions. The lossless component of the scheme partitions the input image into a number of non-overlapping rectangles using a new line-by-line method. The upper-left and the lower-right vertices of each rectangle are identified and the coordinates of which are efficiently encoded using three methods of representation and compression. The lossy component, on the other hand, provides higher compression through two techniques. 1 It reduces the number of rectangles from the input image using our mathematical regression models. These mathematical models guarantees image quality so that rectangular reduction should not produce visual distortion in the image. The mathematical models have been obtained through subjective tests and regression analysis on a large set of binary images. 2 Further compression gain is achieved through discarding isolated pixels and 1-pixel rectangles from the image. Simulation results show that the proposed schemes provide significant improvements over previously published work for both the lossy and the lossless components.