Miracle-dz/UniFAR-FTUs huggingface dataset:
Dendritic Cell Editing by Activated Natural Killer Cells Results in a More Protective Cancer-Specific Immune Response

Over the last decade, several studies have extensively reported that activated natural killer (NK) cells can kill autologous immature dendritic cells (DCs) in vitro, whereas they spare fully activated DCs. This led to the proposal that activated NK cells might select a more immunogenic subset of DCs during a protective immune response. However, there is no demonstration that autologous DC killing by NK cells is an event occurring in vivo and, consequently, the functional relevance of this killing remains elusive. Here we report that a significant decrease of CD11c+ DCs was observed in draining lymph nodes of mice inoculated with MHC-devoid cells as NK cell targets able to induce NK cell activation. This in vivo DC editing by NK cells was perforin-dependent and it was functionally relevant, since residual lymph node DCs displayed an improved capability to induce T cell proliferation. In addition, in a model of anti-cancer vaccination, the administration of MHC-devoid cells together with tumor cells increased the number of tumor-specific CTLs and resulted in a significant increase in survival of mice upon challenge with a lethal dose of tumor cells. Depletion of NK cells or the use of perforin knockout mice strongly decreased the tumor-specific CTL expansion and its protective role against tumor cell challenge. As a whole, our data support the hypothesis that NK cell-mediated DC killing takes place in vivo and is able to promote expansion of cancer-specific CTLs. Our results also indicate that cancer vaccines could be improved by strategies aimed at activating NK cells.
Characteristics of a cell line established from a patient with multiple osteosarcoma, appearing 13 years after treatment for bilateral retinoblastoma

An osteosarcoma cell line, OHS, was established from a patient with multiple skeletal manifestations of osteosarcoma, developing after bilateral retinoblastoma. The tumor cells expressed sarcoma‐associated antigens and showed rapid growth in monolayers and as multicellular spheroids. They formed distinct colonies in soft agar, and subcutaneous tumors in nude mice. Morphological studies indicated that OHS cells had retained important characteristics of the cells of origin. No deletion of the retinoblastoma genes on chromosome 13q 14 could be demonstrated with the banding techniques used. However, cytogenetic studies revealed double minute chromosomes, as evidence of gene amplification, as well as translocations involving chromosomes 1,6,11 and 13. The OHS line can be used to study the genetic basis of tumor initiation and growth, and to elucidate factors predisposing for second primary cancers in retinoblastoma patients.
Stability of Multicluster Synchronization

A system of many coupled oscillators on a network can show multicluster synchronization. We obtain existence conditions and stability bounds for such a multicluster synchronization. When the oscillators are identical, we obtain the interesting result that network structure alone can cause multicluster synchronization to emerge even when all the other parameters are the same. We also study occurrence of multicluster synchronization when two different types of oscillators are coupled.
Intracranial Aneurysm Risk Locus 5q23.2 Is Associated with Elevated Systolic Blood Pressure

Although genome-wide association studies (GWAS) have identified hundreds of complex trait loci, the pathomechanisms of most remain elusive. Studying the genetics of risk factors predisposing to disease is an attractive approach to identify targets for functional studies. Intracranial aneurysms (IA) are rupture-prone pouches at cerebral artery branching sites. IA is a complex disease for which GWAS have identified five loci with strong association and a further 14 loci with suggestive association. To decipher potential underlying disease mechanisms, we tested whether there are IA loci that convey their effect through elevating blood pressure (BP), a strong risk factor of IA. We performed a meta-analysis of four population-based Finnish cohorts (nFIN = 11 266) not selected for IA, to assess the association of previously identified IA candidate loci (n = 19) with BP. We defined systolic BP (SBP), diastolic BP, mean arterial pressure, and pulse pressure as quantitative outcome variables. The most significant result was further tested for association in the ICBP-GWAS cohort of 200 000 individuals. We found that the suggestive IA locus at 5q23.2 in PRDM6 was significantly associated with SBP in individuals of European descent (pFIN = 3.01E-05, pICBP-GWAS = 0.0007, pALL = 8.13E-07). The risk allele of IA was associated with higher SBP. PRDM6 encodes a protein predominantly expressed in vascular smooth muscle cells. Our study connects a complex disease (IA) locus with a common risk factor for the disease (SBP). We hypothesize that common variants in PRDM6 can contribute to altered vascular wall structure, hence increasing SBP and predisposing to IA. True positive associations often fail to reach genome-wide significance in GWAS. Our findings show that analysis of traditional risk factors as intermediate phenotypes is an effective tool for deciphering hidden heritability. Further, we demonstrate that common disease loci identified in a population isolate may bear wider significance.
Prevalence and outcomes of multimorbidity in South Asia: a systematic review

Objective To systematically review the studies of prevalence, patterns and consequences of multimorbidity reported from South Asia. Design Systematic review. Setting South Asia. Data sources Articles were retrieved from two electronic databases (PubMed and Embase) and from the relevant references lists. Methodical data extraction according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines was followed. English-language studies published between 2000 and March 2015 were included. Eligibility criteria Studies addressing prevalence, consequences and patterns of multimorbidity in South Asia. Articles documenting presence of two or more chronic conditions were included in the review. The quality and risk of bias were assessed using STROBE criteria. Data selection Two reviewers independently assessed studies for eligibility, extracted data and assessed study quality. Due to heterogeneity in methodologies among reported studies, only narrative synthesis of the results was carried out. Results Of 11 132, 61 abstracts were selected and 13 were included for final data synthesis. The number of health conditions analysed per study varied from 7 to 22, with prevalence of multimorbidity from 4.5% to 83%. The leading chronic conditions were hypertension, arthritis, diabetes, cardiac problems and skin diseases. The most frequently reported outcomes were increased healthcare utilisation, lowered physical functioning and quality of life, and psychological distress. Conclusions Our study, a comprehensive mapping of multimorbidity research in South Asia, reveals the insufficient volume of work carried out in this domain. The published studies are inadequate to provide an indication of the magnitude of multimorbidity in these countries. Research into clinical and epidemiological aspects of multimorbidity is warranted to build up scientific evidence in this geographic region. The wide heterogeneity observed in the present review calls for greater methodological rigour while conducting these epidemiological studies. Trial registration number CRD42013005456.
Accurate Lungs Segmentation on CT Chest Images by Adaptive Appearance-Guided Shape Modeling

To accurately segment pathological and healthy lungs for reliable computer-aided disease diagnostics, a stack of chest CT scans is modeled as a sample of a spatially inhomogeneous joint 3D Markov-Gibbs random field (MGRF) of voxel-wise lung and chest CT image signals (intensities). The proposed learnable MGRF integrates two visual appearance sub-models with an adaptive lung shape submodel. The first-order appearance submodel accounts for both the original CT image and its Gaussian scale space (GSS) filtered version to specify local and global signal properties, respectively. Each empirical marginal probability distribution of signals is closely approximated with a linear combination of discrete Gaussians (LCDG), containing two positive dominant and multiple sign-alternate subordinate DGs. The approximation is separated into two LCDGs to describe individually the lungs and their background, i.e., all other chest tissues. The second-order appearance submodel quantifies conditional pairwise intensity dependencies in the nearest voxel 26-neighborhood in both the original and GSS-filtered images. The shape submodel is built for a set of training data and is adapted during segmentation using both the lung and chest appearances. The accuracy of the proposed segmentation framework is quantitatively assessed using two public databases (ISBI VESSEL12 challenge and MICCAI LOLA11 challenge) and our own database with, respectively, 20, 55, and 30 CT images of various lung pathologies acquired with different scanners and protocols. Quantitative assessment of our framework in terms of Dice similarity coefficients, 95-percentile bidirectional Hausdorff distances, and percentage volume differences confirms the high accuracy of our model on both our database (98.4±1.0%, 2.2±1.0 mm, 0.42±0.10%) and the VESSEL12 database (99.0±0.5%, 2.1±1.6 mm, 0.39±0.20%), respectively. Similarly, the accuracy of our approach is further verified via a blind evaluation by the organizers of the LOLA11 competition, where an average overlap of 98.0% with the expert's segmentation is yielded on all 55 subjects with our framework being ranked first among all the state-of-the-art techniques compared.
The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling

Despite an enormous interest in the role of extracellular vesicles, including exosomes, in cancer and their use as biomarkers for diagnosis, prognosis, drug response and recurrence, there is no consensus on dependable isolation protocols. We provide a comparative evaluation of 4 exosome isolation protocols for their usability, yield and purity, and their impact on downstream omics approaches for biomarker discovery. OptiPrep density gradient centrifugation outperforms ultracentrifugation and ExoQuick and Total Exosome Isolation precipitation in terms of purity, as illustrated by the highest number of CD63-positive nanovesicles, the highest enrichment in exosomal marker proteins and a lack of contaminating proteins such as extracellular Argonaute-2 complexes. The purest exosome fractions reveal a unique mRNA profile enriched for translation, ribosome, mitochondrion and nuclear lumen function. Our results demonstrate that implementation of high purification techniques is a prerequisite to obtain reliable omics data and identify exosome-specific functions and biomarkers.
Space-Time Water-Filling for Composite MIMO Fading Channels

We analyze the ergodic capacity and channel outage probability for a composite MIMO channel model, which includes both fast fading and shadowing effects. The ergodic capacity and exact channel outage probability with space-time water-filling can be evaluated through numerical integrations, which can be further simplified by using approximated empirical eigenvalue and maximal eigenvalue distribution of MIMO fading channels. We also compare the performance of space-time water-filling with spatial water-filling. For MIMO channels with small shadowing effects, spatial water-filling performs very close to space-time water-filling in terms of ergodic capacity. For MIMO channels with large shadowing effects, however, space-time water-filling achieves significantly higher capacity per antenna than spatial water-filling at low to moderate SNR regimes, but with a much higher channel outage probability. We show that the analytical capacity and outage probability results agree very well with those obtained from Monte Carlo simulations.
Increasing exercise tolerance of persons limited by claudication pain using polestriding.

OBJECTIVE The efficacy of polestriding exercise (walking with modified ski poles with a movement pattern similar to cross-country skiing) to increase exercise tolerance of persons with intermittent claudication pain caused by peripheral arterial disease was tested in this 24-week prospective randomized clinical trial. METHODS The study was conducted in a Department of Veterans Affairs Hospital with 52 individuals who gave written informed consent and were randomized into either a polestriding exercise (n = 27; age, 65.5 +/- 7.0 years; ankle brachial index, 0.64 +/- 0.25) or nonexercise control (n = 25; age, 68.6 +/- 8.9 years; ankle brachial index, 0.69 +/- 0.14) group (P >.05 for all comparisons). The polestriding exercise program consisted of supervised training three times per week for 4 weeks, two times per week for 8 weeks, one time per week for 4 weeks, biweekly for 4 weeks and unsupervised training for 4 weeks. Starting in week 5, subjects took their poles home with instructions to repeat the most recent supervised training walk at an appropriate and convenient location near their residence. This was referred to as unsupervised but directed exercise. Subjects were provided with a personal log book for documenting unsupervised exercise sessions. With both supervised and unsupervised exercise, subjects were expected to complete a total of four 30-minute to 45-minute polestriding exercise sessions per week. The main outcome measures were exercise duration on symptom-limited incremental treadmill test, Walking Impairment Questionnaire, rating of perceived leg pain at baseline, 4, 8, 12, 16, and 24 weeks, and constant work-rate treadmill exercise tests at baseline and at 4, 12, and 24 weeks. RESULTS Polestriding significantly (P <.001) improved exercise tolerance on the constant work-rate and incremental treadmill tests. Ratings of perceived claudication pain were significantly less after the polestriding training program. Subject perceived distance and walking speed scores on the Walking Impairment Questionnaire improved in the polestriding trained group only (P <.001 and.022, respectively). CONCLUSION This randomized clinical trial provides empirical evidence that 24 weeks of polestriding training significantly improves quantitative and qualitative measures of the exercise tolerance of persons limited by intermittent claudication pain.
A Hydrophobic Stretch of 12 Amino Acid Residues in the Middle of α-Synuclein Is Essential for Filament Assembly*

Neuronal and oligodendrocytic aggregates of fibrillar α-synuclein define several diseases of the nervous system. It is likely that these inclusions impair vital metabolic processes and compromise vialibity of affected cells. Here, we report that a 12-amino acid stretch (71VTGVTAVAQKTV82) in the middle of the hydrophobic domain of human α-synuclein is necessary and sufficient for its fibrillization based on the following observations: 1) human β-synuclein is highly homologous to α-synuclein but lacks these 12 residues, and it does not assemble into filaments in vitro; 2) the rate of α-synuclein polymerization in vitro decreases after the introduction of a single charged amino acid within these 12 residues, and a deletion within this region abrogates assembly; 3) this stretch of 12 amino acids appears to form the core of α-synuclein filaments, because it is resistant to proteolytic digestion in α-synuclein filaments; and 4) synthetic peptides corresponding to this 12-amino acid stretch self-polymerize to form filaments, and these peptides promote fibrillization of full-length human α-synuclein in vitro. Thus, we have identified key sequence elements necessary for the assembly of human α-synuclein into filaments, and these elements may be exploited as targets for the design of drugs that inhibit α-synuclein fibrillization and might arrest disease progression.
A Multi-level Thresholding Approach Based on Group Search Optimization Algorithm and Otsu

Image Segmentation is a key process in image analysis and computer vision. Otsu is a simple but effective thresholding method, which is widely used for image segmentation. However, when one-dimensional Otsu is generalized to multi-threshold, the increased amount of computation will break down its efficiency and limits its application. Some evolutionary algorithms haven utilized to speed up the basic multi-level Otsu, such as genetic algorithm, particle swarm optimization, differential evolution algorithm etc, but these algorithms are easy to trap into the local optima. In the paper, in order to reduce computation and obtain the optimal thresholding values, the group search optimizer (GSO) algorithm is employed to optimize the basic Otsu thresholding method. The presented approach has been tested on some standard images and compared with other evolutionary algorithms in terms of fitness value. Experimental results prove that GSO is robust and superior to the other methods involved in the paper.
Clinical features and treatment outcomes of pediatric acute promyelocytic leukemia in a Mexican pediatric hospital.

INTRODUCTION Acute promyelocytic leukemia (APL) is a distinct type of acute myeloid leukemia (AML) characterized by chromosomal translocations involving the retinoid acid receptor α (RARA) gene on chromosome 17. APL is a relatively rare blood disease that is highly curable with current treatment strategies; however, patient outcomes are heterogeneous in countries with limited resources. Promyelocytic leukemia accounts for 20-25% of all AML cases in Latin American countries. MATERIAL AND METHODS We conducted a study from July 2007 to July 2012 and applied the IC-APL2006 protocol. This case study reports the results from eleven patients with AML M3 (five males and six females). In all cases, the diagnoses were made by aspirating bone marrow and evaluating the t(15:17) or t(11:17) transcript. In eight cases, the molecular biology-based diagnostics for the PLM-RARa transcript were positive, and they were negative in two cases. One patient was positive for the PLZF-RARa transcript. RESULTS The mean WBC at the time of diagnosis was 10.1 x 10(9)/L, and the mean platelet count was 17.1 x 10(9)/L. The mean percentage of abnormal promyelocytes in the bone marrow aspirates was 68%. Of the eleven patients, four presented with disseminated intravascular coagulation. All of the patients began treatment with transretinoic acid (ATRA) (45 mg/m(2)/day), which led to 4 cases of ATRA syndrome. There were 2 relapses, and the patient died in one case. The remaining ten patients were alive after the median follow-up period of 33.6 months (range from 11 to 60 months). CONCLUSION The authors report on a series of cases involving pediatric patients with AML M3 seen at a single institution; the patients were stratified and treated with a standard protocol to obtain satisfactory results. Although the number of patients is limited, the health outcomes are relevant. To our knowledge, this is the first series of pediatric APL patients in Mexico who were treated with the IC-APL2006 protocol.
Inferring models of concurrent systems from logs of their behavior with CSight

Concurrent systems are notoriously difficult to debug and understand. A common way of gaining insight into system behavior is to inspect execution logs and documentation. Unfortunately, manual inspection of logs is an arduous process, and documentation is often incomplete and out of sync with the implementation. To provide developers with more insight into concurrent systems, we developed CSight. CSight mines logs of a system's executions to infer a concise and accurate model of that system's behavior, in the form of a communicating finite state machine (CFSM). Engineers can use the inferred CFSM model to understand complex behavior, detect anomalies, debug, and increase confidence in the correctness of their implementations. CSight's only requirement is that the logged events have vector timestamps. We provide a tool that automatically adds vector timestamps to system logs. Our tool prototypes are available at http://synoptic.googlecode. com/. This paper presents algorithms for inferring CFSM models from traces of concurrent systems, proves them correct, provides an implementation, and evaluates the implementation in two ways: by running it on logs from three different networked systems and via a user study that focused on bug finding. Our evaluation finds that CSight infers accurate models that can help developers find bugs.
Report of MIRACLE team for the Ad-Hoc Track in CLEF 2007

This paper presents the 2006 MIRACLE’s team approach to the AdHoc Information Retrieval track. The experiments for this campaign keep on testing our IR approach. First, a baseline set of runs is obtained, including standard components: stemming, transforming, filtering, entities detection and extracting, and others. Then, a extended set of runs is obtained using several types of combinations of these baseline runs. The improvements introduced for this campaign have been a few ones: we have used an entity recognition and indexing prototype tool into our tokenizing scheme, and we have run more combining experiments for the robust multilingual case than in previous campaigns. However, no significative improvements have been achieved. For the this campaign, runs were submitted for the following languages and tracks: - Monolingual: Bulgarian, French, Hungarian, and Portuguese. - Bilingual: English to Bulgarian, French, Hungarian, and Portuguese; Spanish to French and Portuguese; and French to Portuguese. - Robust monolingual: German, English, Spanish, French, Italian, and Dutch. - Robust bilingual: English to German, Italian to Spanish, and French to Dutch. - Robust multilingual: English to robust monolingual languages. We still need to work harder to improve some aspects of our processing scheme, being the most important, to our knowledge, the entities recognition and normalization.
An experimental study on hurricane mesovortices

Mesovortices in the eyewall region of a hurricane are intriguing elements of the hurricane engine. In-situ measurements of them are sparse, however, and our understanding of their overall role in the physics of a hurricane is incomplete. To further understand their dynamics an experimental apparatus using a homogeneous fluid (water) has been constructed to emulate the lower tropospheric flow of the hurricane eye/eyewall region. For experimental configurations possessing a central aspect ratio less than unity, a primary and secondary circulation similar to the in flow layer of an intense hurricane, and a similar radius-to-width ratio of the curvilinear shear layer bordering the eye and eyewall region, the flow supports two primary quasi-steady vortices and secondary intermittent vortices. The vortices form through Kelvin–Helmholtz instability of the curvilinear shear layer bordering the slowly upwelling fluid in the centre and the converging fluid from the periphery. The primary vortices are maintained by convergence of circulation from the periphery and merger of secondary vortices spawned along the shear layer. The horizontal flow field is measured using a particle image velocimeter. Despite the relatively strong secondary circulation through the parent vortex the horizontal flow is found to be approximately uniform in the direction parallel to the rotation axis. The peak tangential velocity is found to occur in the mesovortices and is roughly 50% greater than the parent vortex that supports them. The measurements provide insight into recent observations of excessive wind damage in landfalling storms and support the hypothesis that intense storms contain coherent vortex structures in the eyewall region with higher horizontal wind speeds locally than the parent hurricane.