Miracle-dz/UniFAR-FTUs huggingface dataset:
Variation at NOD2/CARD15 in familial and sporadic cases of Crohn's disease in the Ashkenazi Jewish population

OBJECTIVE:Recent reports indicate that allelic variants in NOD2/CARD15 are associated with Crohn's disease (CD) susceptibility, and that homozygosity or compound heterozygosity at this locus for any of three recently defined sequence variants confers a greatly increased risk of CD. These sequence changes include two missense mutations, R702W and G908R, and a frameshift insertion, 1007insC. The aim of this study was to determine the frequency of these NOD2/CARD15 variants in familial and sporadic CD patients in the Ashkenazi population and to determine their effects on disease susceptibility and age of disease onset (AOO). METHODS:Allele and genotype frequencies of these three variants were determined in 481 CD patients of Jewish descent and 110 Jewish controls; 169 patients had a family history of CD, and 312 were “sporadic” cases. Variants were detected by polymerase chain reaction using allele-specific primers labeled with fluorescent dye.RESULTS:Familial cases had a significantly higher frequency of the G908R variant than sporadic cases (0.127 vs 0.059, p = 0.0003) and correspondingly, a significantly higher proportion of homozygotes and compound heterozygotes (11.8% vs 4.5%, p = 0.0027). Homozygotes and compound heterozygotes had an OR for CD of 14.6 for familial cases and 5.1 for sporadic cases. There was no increased risk of CD for simple heterozygotes. The AOO was significantly lower for CD patients who were homozygotes and compound heterozygotes for NOD2/CARD15 (17.5 vs 22.4 yr, p = 0.04), but only for familial cases.CONCLUSIONS:NOD2/CARD15 contributes more to CD susceptibility in familial cases than in sporadic cases, and to an earlier AOO. There is no increased risk of CD for individuals carrying only a single copy of these NOD2/CARD15 variants, whereas individuals carrying two copies have a 5–15-fold increased risk. The penetrance of the NOD2/CARD15 mutations was estimated at less than 1%.
Leucocyte telomere length in patients with sickle cell disease

Beavis, P.A. , Stagg, J., Darcy, P.K. & Smyth, M.J. (2012) CD73: a potent suppressor of antitumor immune responses. Trends in Immunology, 33, 231–237. Buggins, A.G. , Milojkovic, D. , Arno, M.J., Lea, N.C. , Mufti, G.J., Thomas, N.S. & Hirst, W.J. (2001) Microenvironment produced by acute myeloid leukemia cells prevents T cell activation and proliferation by inhibition of NF-kappaB, c-Myc, and pRb pathways. The Journal of Immunology, 167, 6021–6030. Estey, E. & Dohner, H. (2006) Acute myeloid leukaemia. Lancet, 368, 1894–1907. Hausler, S.F. , Montalban del Barrio, I. , Strohschein, J., Anoop Chandran, P., Engel, J.B. , Honig, A. , Ossadnik, M. , Horn, E. , Fischer, B. , Krockenberger, M. , Heuer, S. , Seida, A.A. , Junker, M. , Kneitz, H. , Kloor, D. , Klotz, K.N. , Dietl, J. & Wischhusen, J. (2011) Ectonucleotidases CD39 and CD73 on OvCA cells are potent adenosine-generating enzymes responsible for adenosine receptor 2A-dependent suppression of T cell function and NK cell cytotoxicity. Cancer immunology, immunotherapy: CII, 60, 1405– 1418. Miyara, M. , Yoshioka, Y. , Kitoh, A. , Shima, T. , Wing, K. , Niwa, A. , Parizot, C. , Taflin, C. , Heike, T. , Valeyre, D. , Mathian, A. , Nakahata, T. , Yamaguchi, T. , Nomura, T. , Ono, M. , Amoura, Z. , Gorochov, G. & Sakaguchi, S. (2009) Functional delineation and differentiation dynamics of human CD4 + T cells expressing the FoxP3 transcription factor. Immunity, 30, 899–911. Nikolova, M. , Carriere, M. , Jenabian, M.A., Limou, S. , Younas, M. , Kok, A. , Hue, S. , Seddiki, N. , Hulin, A. , Delaneau, O. , Schuitemaker, H. , Herbeck, J.T. , Mullins, J.I. , Muhtarova, M. , Bensussan, A. , Zagury, J.F. , Lelievre, J.D. & Levy, Y. (2011) CD39/adenosine pathway is involved in AIDS progression. PLoS pathogens, 7, e1002110. Schick, J., Vogt, V. , Zerwes, M. , Kroell, T. , Kraemer, D. , Kohne, C.H. , Hausmann, A. , Buhmann, R. , Tischer, J. & Schmetzer, H. (2013) Antileukemic T-cell responses can be predicted by the composition of specific regulatory T-cell subpopulations. Journal of immunotherapy, 36, 223–237. Serra, S. , Horenstein, A.L. , Vaisitti, T. , Brusa, D. , Rossi, D. , Laurenti, L. , D’Arena, G. , Coscia, M. , Tripodo, C. , Inghirami, G. , Robson, S.C. , Gaidano, G. , Malavasi, F. & Deaglio, S. (2011) CD73-generated extracellular adenosine in chronic lymphocytic leukemia creates local conditions counteracting drug-induced cell death. Blood, 118, 6141–6152. Shenghui, Z. , Yixiang, H. , Jianbo, W. , Kang, Y. , Laixi, B. , Yan, Z. & Xi, X. (2011) Elevated frequencies of CD4(+) CD25(+) CD127lo regulatory T cells is associated to poor prognosis in patients with acute myeloid leukemia. International journal of cancer, 129, 1373–1381. Szczepanski, M.J., Szajnik, M. , Czystowska, M. , Mandapathil, M. , Strauss, L. , Welsh, A. , Foon, K.A. , Whiteside, T.L. & Boyiadzis, M. (2009) Increased frequency and suppression by regulatory T cells in patients with acute myelogenous leukemia. Clinical cancer research, 15, 3325– 3332.
The Roles of Whole-Genome and Small-Scale Duplications in the Functional Specialization of Saccharomyces cerevisiae Genes

Researchers have long been enthralled with the idea that gene duplication can generate novel functions, crediting this process with great evolutionary importance. Empirical data shows that whole-genome duplications (WGDs) are more likely to be retained than small-scale duplications (SSDs), though their relative contribution to the functional fate of duplicates remains unexplored. Using the map of genetic interactions and the re-sequencing of 27 Saccharomyces cerevisiae genomes evolving for 2,200 generations we show that SSD-duplicates lead to neo-functionalization while WGD-duplicates partition ancestral functions. This conclusion is supported by: (a) SSD-duplicates establish more genetic interactions than singletons and WGD-duplicates; (b) SSD-duplicates copies share more interaction-partners than WGD-duplicates copies; (c) WGD-duplicates interaction partners are more functionally related than SSD-duplicates partners; (d) SSD-duplicates gene copies are more functionally divergent from one another, while keeping more overlapping functions, and diverge in their sub-cellular locations more than WGD-duplicates copies; and (e) SSD-duplicates complement their functions to a greater extent than WGD–duplicates. We propose a novel model that uncovers the complexity of evolution after gene duplication.
Method for Recovery and Immunoaffinity Enrichment of Membrane Proteins Illustrated with Metastatic Ovarian Cancer Tissues

Integral membrane proteins play key biological roles in cell signaling, transport, and pathogen invasion. However, quantitative clinical assays for this critical class of proteins remain elusive and are generally limited to serum-soluble extracellular fragments. Furthermore, classic proteomic approaches to membrane protein analysis typically involve proteolytic digestion of the soluble pieces, resulting in separation of intra- and extracellular segments and significant informational loss. In this paper, we describe the development of a new method for the quantitative extraction of intact integral membrane proteins (including GPCRs) from solid metastatic ovarian tumors using pressure cycling technology in combination with a new (ProteoSolve-TD) buffer system. This new extraction buffer is compatible with immunoaffinity methods (e.g., ELISA and immunoaffinity chromatography), as well as conventional proteomic techniques (e.g., 2D gels, western blots). We demonstrate near quantitative recovery of membrane proteins EDG2, EDG4, FASLG, KDR, and LAMP-3 by western blots. We have also adapted commercial ELISAs for serum-soluble membrane protein fragments (e.g., sVEGFR2) to measure the tissue titers of their transmembrane progenitors. Finally, we demonstrate the compatibility of the new buffers with immunoaffinity enrichment/mass spectrometric characterization of tissue proteins.
The Families of Schizophrenic Patients

My first study dealing with families of schizophrenic patients was confined to the mothers and to the mother-child relationship in schizophrenia. Employing the psychiatric interview, I investigated the mothers of 100 schizophrenic patients under 30 years of age, and the mothers of 20 neurotic patients and of 20 normal controls. The Rorschach test was administered to 92 of the mothers of schizophrenics and to all mothers in the control series. In a monograph (Alanen 1958) I classified the mothers I had studied into clinical categories on a unidimensional scale. The distribution that resulted is illustrated in Table 1. I found that 12 ofthe mothers of schizophrenics had been manifestly psychotic and that a further 11 displayed, unrealistic thought and behaviour patterns bordering on the psychotic. These mothers were assigned to the diagnostic categories A and B respectively. The most impressive finding, in my opinion, was the high frequency of mothers who were not included either in the psychotic or in the borderline group but were
Preliminary evidence of asymmetry in uncomfortable loudness levels after unilateral hearing aid experience: Evidence of functional plasticity in the adult auditory system

The aim of the study was to compare uncomfortable loudness levels (ULLs) in a group of adults before and after unilateral hearing aid experience. Twelve participants presented with a symmetrical hearing loss consistent with natural ageing. Pure tones were presented to each ear separately, commencing at 60 dB HL and increased in 5-dB step sizes until ULL was reached. The post-fitting ULLs were typically measured three years after fitting. Hearing thresholds were symmetrical and remained unchanged after fitting. Mean ULL values were symmetrical before fitting. The mean ULL values increased (i.e. greater tolerance) in both ears after fitting; however, the increase was greatest in the fitted ear: 14.5 and 7 dB at 2000–4000 Hz in the fitted and not-fitted ear, respectively. A separate two-factor repeated ANOVA (ear and frequency) was performed on the pre and post-fitting ULL data. There was no statistically significant difference for ear (p > 0.05) when comparing the pre-fitting ULLs. However, there was a statistically significant difference for ear (p < 0.01) when comparing post-fitting ULLs. The underlying mechanism for the asymmetry is unknown but it is consistent with learning induced reorganization within the auditory system.
Gender inequality in acute coronary syndrome patients at Omdurman Teaching Hospital, Sudan

Background: Gender differences among patients with the acute coronary syndrome is still being debated, no research has been done on gender inequality among coronary syndrome patients in Sudan. Objectives: To study gender differences in presentation, management, and outcomes of acute coronary syndrome in Sudan. Subjects and Methods: This cross-sectional descriptive longitudinal study was conducted in Omdurman Teaching Hospital between July 2014 and August 2015. Patients were invited to sign a written informed consent form, were interviewed and examined by a physician, and then followed during their hospital stay. Information collected includes coronary risk factors, vital signs, echocardiography findings, arrhythmias, heart failure, cardiogenic shock, and death. The Ethical Committee of Omdurman Teaching Hospital approved the research. Results: A total of 197 consecutive acute coronary syndrome patients were included, 43.1% were females. A significant statistical difference was evident between males and females regarding the type of acute coronary syndrome, its presentation, and time of presentation to the hospital, smoking, and receipt of thrombolysis (P < 0.05). No differences were found with regard to age, hypertension, diabetes, family history of myocardial infarction, percutaneous coronary intervention, and in-hospital acute coronary complications (P > 0.05). Conclusion: Women were less likely to receive thrombolytic therapy, present with chest pain, and diagnosed with ST-segment elevation myocardial infarction. No gender differences were found in acute coronary syndrome risk factors apart from smoking, which was more common in males, and there were no differences between males and females as regards in-hospital complications.
Change Detection from a Street Image Pair using CNN Features and Superpixel Segmentation

Figures 1 100 show the results of the scenes of Panoramic Change Detection Dataset. The rows show, from top to bottom, input image pair, ground-truth of change detection, final change detection results, superpixel segmentation results, feature distance between each grid using feature of pool-5 layer, feature distance projected to superpixel segmentation result of each input image, probabilities of the sky and the ground estimated using Geometric Context.
Primary Human Airway Epithelial Cell-Dependent Inhibition of Human Lung Mast Cell Degranulation

Introduction Chronic mast cell activation is a characteristic feature of asthma. BEAS-2B human airway epithelial cells (AEC) profoundly inhibit both constitutive and IgE-dependent human lung mast cell (HLMC) histamine release. The aim of this study was to examine the regulation of HLMC degranulation by primary AEC from healthy and asthmatic subjects, and investigate further the inhibitory mechanism. Methods HLMC were co-cultured with both BEAS-2B and primary AEC grown as monolayers or air-liquid interface (ALI) cultures. Results Both constitutive and IgE-dependent HLMC histamine release were attenuated by BEAS-2B, primary AEC monolayers and ALI cultures. This occurred in the absence of HLMC-AEC contact indicating the presence of a soluble factor. Unlike healthy ALI AEC, asthmatic ALI-AEC did not significantly reduce constitutive histamine release. AEC inhibitory activity was transferable in primary AEC monolayer supernatant, but less active than with Transwell co-culture, suggesting that the inhibitory factor was labile. The AEC inhibitory effects were attenuated by both AEC wounding and pertussis toxin, indicating the involvement of a G0/Gi receptor coupled mechanism. Solid phase extraction of lipids (<10 kDa) removed the AEC inhibitory activity. The lipid derivatives resolvin D1 and D2 and lipoxin A4 attenuated HLMC histamine release in a dose-dependent fashion but were not detectable in co-culture supernatants. Conclusions Primary AEC suppress HLMC constitutive and IgE-dependent histamine secretion through the release of a soluble, labile lipid mediator(s) that signals through the G0/Gi receptor coupled mechanism. Manipulation of this interaction may have a significant therapeutic role in asthma.
A Tyr368His RPE65 founder mutation is associated with variable expression and progression of early onset retinal dystrophy in 10 families of a genetically isolated population

Autosomal recessive retinal dystrophies cause visual impairment in approximately 1 in 4000 individuals worldwide.1 The non-syndromic forms are highly heterogeneous and can be classified into clinical subgroups, the most frequent ones being retinitis pigmentosa, cone and cone-rod dystrophies, and Leber congenital amaurosis (LCA). LCA represents the most severe phenotype with an onset of symptoms before the age of six months, visual acuity below 20/400, a searching nystagmus, sluggish pupillary reactions, and a non-detectable electroretinogram (ERG). Visual fields are usually not measurable.1 Photophobia is only occasionally reported in LCA.2 Patients with juvenile and early onset retinitis pigmentosa present with night blindness in early childhood, usually before the age of two years. They do not show searching nystagmus3 and have a relatively well preserved macular function. Central vision is often lost in the second or third decade of life.4 The cloning of more than 20 genes allows the molecular characterisation of approximately 50% of the autosomal recessive inherited retinal dystrophy cases (http://www.sph.uth.tmc.edu/Retnet5,6 ). To establish a useful clinical prognosis for patients a well defined genotype–phenotype correlation is required. Although the general population in the Netherlands is relatively outbred, there are a few examples of autosomal recessive diseases caused by Dutch founder mutations. Batten disease was found to be due to identity-by-descent in a highly inbred family.7 A frequent LDL receptor mutation originating from Dutch 17th century settlers causes familial hypercholesterolaemia in South Africa and Canada.8 The RP12 locus was mapped through linkage analysis in a genetic isolate from the northwest of the Netherlands,9 which was followed by the cloning of the underlying gene, CRB1 . 10 In 1959 Schappert-Kimmijser et al described an isolated Dutch population living on a former island with a relatively high frequency of LCA.11 In 1637 this …
Incorporating Similarity and Trust for Collaborative Filtering

Currently, most recommender systems are using collaborative filtering (CF) techniques. The main idea is to suggest new relevant items for an active user based on the judgements from other members in the like-minded community. However, these CF-based methods encounter the obstacles, such as sparse data, cold-start and robustness. This paper proposes to deal with these issues by associating similarity measurement from users’rating patterns with trust metric. After investigating the large data set from Epinions.com, we find that user similarity and trust are strongly correlated. This fact also explains why using trust (instead of user similarity) could lead to very close mean prediction accuracy in a Pearson Correlation Coefficient-like recommendation algorithm. Our novel method incorporates these two factors into one unified recommendation algorithm. The experimental results indicate that a good prediction strategy can come from filtering the ratings from the users who have high trust and low similarity or vice versa.
SNR Estimation for Multi-dimensional Cognitive Receiver under Correlated Channel/Noise

In addition to Spectrum Sensing (SS) capability required by a Cognitive Radio (CR), Signal to Noise Ratio (SNR) estimation of the primary signals at the CR receiver is crucial in order to adapt its coverage area dynamically using underlay techniques. In practical scenarios, channel and noise may be correlated due to various reasons and SNR estimation techniques with the assumption of white noise and uncorrelated channel may not be suitable for estimating the primary SNR. In this paper, firstly, we study the performance of different eigenvalue-based SS techniques in the presence of channel or/and noise correlation. Secondly, we carry out detailed theoretical analysis of the signal plus noise hypothesis to derive the asymptotic eigenvalue probability distribution function (a.e.p.d.f.) of the received signal's covariance matrix under the following two cases: (i) correlated channel and white noise, and (ii) correlated channel and correlated noise, which is the main contribution of this paper. Finally, an SNR estimation technique based on the derived a.e. p.d. f is proposed in the presence of channel/noise correlation and its performance is evaluated in terms of normalized Mean Square Error (MSE). It is shown that the PU SNR can be reliably estimated when the CR sensing module is aware of the channel/noise correlation.
Chemical Composition and Health Benefits of Flaxseed

Flaxseed or linseed (Linum usitatissimum L.) comes from the flax plant, an annual herb. The main importance of flaxseed is in the human nutrition sector because it is emerging as an important functional food ingredient thanks to the content of active compounds, pointed to provide health benefits. There are several ways to eat flaxseed: milled, in the form of oil or added to bakery product. Scientific evidences support consumption of flaxseed for the high content in omega-3, omega-6 rich oil, α-linolenic acid, lignans, high quality proteins and fibers, compounds which are biologically active in the prevention of some chronic diseases such as many types of cancer, diabetes, cardiovascular diseases and cerebrovascular stroke. Furthermore, advantages in flaxseed consumptions are shown in animal nutrition sector and therefore result in healthier food from animal origin. In fact, the fatty acid profile of the meat and fat is directly affected by the source of fat in diet in swine and poultry, feeding omega-3 enriched diets by the addition of flaxseed would increase the omega-3 content in eggs and meat and thus enrich the products. The present review is focused on recent data on flaxseed chemical composition and its beneficial effects.
Host heterogeneity is a determinant of competitive exclusion or coexistence in genetically diverse malaria infections

During an infection, malaria parasites compete for limited amounts of food and enemy–free space. Competition affects parasite growth rate, transmission and virulence, and is thus important for parasite evolution. Much evolutionary theory assumes that virulent clones outgrow avirulent ones, favouring the evolution of higher virulence. We infected laboratory mice with a mixture of two Plasmodium chabaudi clones: one virulent, the other avirulent. Using real–time quantitative PCR to track the two parasite clones over the course of the infection, we found that the virulent clone overgrew the avirulent clone. However, host genotype had a major effect on the outcome of competition. In a relatively resistant mouse genotype (C57Bl/6J), the avirulent clone was suppressed below detectable levels after 10 days, and apparently lost from the infection. By contrast, in more susceptible mice (CBA/Ca), the avirulent clone was initially suppressed, but it persisted, and during the chronic phase of infection it did better than it did in single infections. Thus, the qualitative outcome of competition depended on host genotype. We suggest that these differences may be explained by different immune responses in the two mouse strains. Host genotype and resistance could therefore play a key role in the outcome of within–host competition between parasite clones and in the evolution of parasite virulence.
The Economics of Solicited and Unsolicited Credit Ratings

This paper develops a dynamic rational expectations model of the credit rating process, incorporating three critical elements of this industry: (i) the rating agencies’ ability to misreport the issuer’s credit quality, (ii) their ability to issue unsolicited ratings, and (iii) their reputational concerns. We analyze the incentives of credit rating agencies to issue unsolicited credit ratings and the eects of this practice on the agencies’ rating strategies. We nd that the issuance of unfavorable unsolicited credit ratings enables rating agencies to extract higher fees from issuers by credibly threatening to punish those that refuse to solicit a rating. Also, issuing unfavorable unsolicited ratings increases the rating agencies’ reputation by demonstrating to investors that they resist the temptation to issue inated ratings. In equilibrium, unsolicited credit ratings are lower than solicited ratings, because all favorable ratings are solicited; however, they do not have a downward bias. We show that, under certain conditions, a credit rating system that incorporates unsolicited ratings leads to more stringent rating standards. Finally, we argue that credit rating standards vary over the business cycle in a countercyclical fashion where economic \booms" are associated with lower standards and are followed by an increase in default rates of highly rated securities.