Miracle-dz/UniFAR-FTUs huggingface dataset:
The genetic landscape of infantile spasms.

Infantile spasms (IS) is an early-onset epileptic encephalopathy of unknown etiology in ∼40% of patients. We hypothesized that unexplained IS cases represent a large collection of rare single-gene disorders. We investigated 44 children with unexplained IS using comparative genomic hybridisation arrays (aCGH) (n = 44) followed by targeted sequencing of 35 known epilepsy genes (n = 8) or whole-exome sequencing (WES) of familial trios (n = 18) to search for rare inherited or de novo mutations. aCGH analysis revealed de novo variants in 7% of patients (n = 3/44), including a distal 16p11.2 duplication, a 15q11.1q13. 1 tetrasomy and a 2q21.3-q22.2 deletion. Furthermore, it identified a pathogenic maternally inherited Xp11.2 duplication. Targeted sequencing was informative for ARX (n = 1/14) and STXBP1 (n = 1/8). In contrast, sequencing of a panel of 35 known epileptic encephalopathy genes (n = 8) did not identify further mutations. Finally, WES (n = 18) was very informative, with an excess of de novo mutations identified in genes predicted to be involved in neurodevelopmental processes and/or known to be intolerant to functional variations. Several pathogenic mutations were identified, including de novo mutations in STXBP1, CASK and ALG13, as well as recessive mutations in PNPO and ADSL, together explaining 28% of cases (5/18). In addition, WES identified 1-3 de novo variants in 64% of remaining probands, pointing to several interesting candidate genes. Our results indicate that IS are genetically heterogeneous with a major contribution of de novo mutations and that WES is significantly superior to targeted re-sequencing in identifying detrimental genetic variants involved in IS.
On the Computability of AIXI

How could we solve the machine learning and the artificial intelligence problem if we had infinite computation? Solomonoff induction and the reinforcement learning agent AIXI are proposed answers to this question. Both are known to be incomputable. In this paper, we quantify this using the arithmetical hierarchy, and prove upper and corresponding lower bounds for in-computability. We show that AIXI is not limit computable, thus it cannot be approximated using finite computation. Our main result is a limit-computable e-optimal version of AIXI with infinite horizon that maximizes expected rewards.
On Discrete Su cient Statistics for Detection in AsynchronousBand-limited CDMA SystemsAshok

The problem of generating discrete suucient statistics for statistical signal processing in Code Division Multiple Access (CDMA) systems is considered in context of the underlying channel bandwidth restrictions. In most analyses of CDMA systems, the derivation of discrete suucient statistics is facilitated by relaxing the bandwidth constraints on the noise and the signaling waveforms. It is shown that relaxing the constraints on the signaling waveforms can produce inaccurate discrete system models leading to anomalous results for detection in asynchronous CDMA systems. This is illustrated by considering the performance analyses of matched lter detection and minimum mean squared error (MMSE) detection. The role of chip-matched ltering in generating accurate discrete suucient statistics is also explored.
T1-weighted three-dimensional magnetization transfer MR of the brain: improved lesion contrast enhancement.

PURPOSE We developed and evaluated clinically T1-weighted three-dimensional gradient-echo magnetization transfer (MT) sequences for contrast-enhanced MR imaging of the brain. METHODS A short-repetition-time, radio frequency-spoiled, 3-D sequence was developed with a 10-millisecond MT pulse at high MT power and narrow MT pulse-frequency offset, and the enhancing lesion-to-normal white matter background (L/B) and the contrast-to-noise (C/N) ratios on these images were compared with those on T1-weighted spin-echo images and on non-MT 3-D gradient-echo images in a prospective study of 45 patients with 62 enhancing lesions. In the 24 patients who had intracranial metastatic disease, the number of lesions was counted and compared on the three types of images. RESULTS The MT ratio of normal callosal white matter was 55% on the MT 3-D gradient-echo sequences. The L/B and C/N on the MT 3-D gradient-echo images were more than double those on the 3-D gradient-echo images, and were significantly greater than those on the T1-weighted spin-echo images. In patients with metastatic disease, the MT 3-D gradient-echo images showed significantly more lesions than did the T1-weighted spin-echo or 3-D gradient-echo images. CONCLUSION MT 3-D gradient-echo MR imaging improves the contrast between enhancing lesion and background white matter over that obtained with conventional T1-weighted 3-D gradient-echo and spin-echo imaging. MT 3-D gradient-echo imaging provides practical sampling, image coverage, and spatial resolution, attributes that may be advantageous over MT T1-weighted spin-echo techniques.
Autoreactive Anti-DNA Transgenic B Cells in Lupus-Prone New Zealand Black/New Zealand White Mice Show Near Perfect L Chain Allelic Exclusion1

Recent work on B cell tolerance and autoimmunity has suggested the L chain allelic inclusion is a property of autoreactive B cells and is closely linked to receptor editing. Allelic inclusion could rescue autoreactive B cells from clonal deletion by reducing their effective BCR surface density. We have investigated this phenomenon in anti-DNA producing hybridomas, derived from different strains of Ig gene-targeted, lupus-prone NZB/NZW mice. Our results indicate that isotype and allelic exclusion was strictly maintained in most high- and low-affinity, edited and nonedited, anti-DNA transgenic B cells. However, a substantial fraction of the anti-DNA hybridomas expressed a very restricted set of nonproductively rearranged L chain mRNA, in addition to the productive anti-DNA L chain. The aberrant L chains could have a role in the selection and survival of autoreactive B cells in these autoimmune mice.
Zoonoses in humans from small rural properties in Jataizinho, Parana, Brazil

The aim of this study was to conduct a serological survey for Lyme diseases, brucellosis, leptospirosis and toxoplasmosis and identify the risk variables related to these zoonoses in humans living in the rural area of Jataizinho, state of Parana, Brazil. A total of 63 rural properties were surveyed. Additionally, 207 serum samples collected from these rural area inhabitants were tested for indirect immunofluorescence (IFI) and western blots (WB) were performed to detect Borrelia burgdorferi (sensu lato); a tamponated acidified antigen test (AAT) and 2-mercaptoethanol (2-ME) were used to detect antibodies of Brucella abortus; the microscopic agglutination test (MAT) was carried out to detect antibodies anti-Leptospira spp. and IFI was used to find antibodies of Toxoplasma gondii. Two of the samples (0.96%) were reactive for Lyme borreliosis, three (1.4%) for brucellosis, 25 (12.1%) for leptospirosis and 143 (69.1%) for toxoplasmosis. Although the town of Jataizinho has a human development index (IDH) that was considered to be average (0.733) in the state of Parana, the low social, economic and cultural conditions of the population from small rural properties have resulted in lack of basic information on animal health and direct or indirect contact with the various species of domestic animals, wildlife and ticks have probably contributed to the prevalence levels found. These results show the need for additional regional studies in order to determine the epidemiological characteristics of these diseases as well as their respective vectors and reservoirs so that effective prophylaxis can be administered in the human population.
Identification and Disruption of lisRK, a Genetic Locus Encoding a Two-Component Signal Transduction System Involved in Stress Tolerance and Virulence in Listeria monocytogenes

ABSTRACT lisRK encodes a two-component regulatory system in the food pathogen Listeria monocytogenes LO28. Following identification of the operon in an acid-tolerant Tn917mutant, a deletion in the histidine kinase component was shown to result in a growth phase variation in acid tolerance, an ability to grow in high ethanol concentrations, and a significant reduction in virulence.
Study of interaction of antimutagenic 1,4-dihydropyridine AV-153-Na with DNA-damaging molecules and its impact on DNA repair activity

Background 1,4-dihydropyridines (1,4-DHP) possesses important biochemical and pharmacological properties, including antioxidant and antimutagenic activities. It was shown that the antimutagenic 1,4-dihydropyridine AV-153-Na interacts with DNA. The aim of the current study was to test the capability of the compound to scavenge peroxynitrite and hydroxyl radical, to test intracellular distribution of the compound, and to assess the ability of the compound to modify the activity of DNA repair enzymes and to protect the DNA in living cells against peroxynitrite-induced damage. Methods Peroxynitrite decomposition was assayed by UV spectroscopy, hydroxyl radical scavenging—by EPR spectroscopy. DNA breakage was determined by the “comet method”, activity of DNA repair enzymes—using Glyco-SPOT and ExSy-SPOT assays. Intracellular distribution of the compound was studied by laser confocal scanning fluorescence microscopy. Fluorescence spectroscopy titration and circular dichroism spectroscopy were used to study interactions of the compound with human serum albumin. Results Some ability to scavenge hydroxyl radical by AV-153-Na was detected by the EPR method, but it turned out to be incapable of reacting chemically with peroxynitrite. However, AV-153-Na effectively decreased DNA damage produced by peroxynitrite in cultured HeLa cells. The Glyco-SPOT test essentially revealed an inhibition by AV-153-Na of the enzymes involved thymine glycol repair. Results with ExSy-SPOT chip indicate that AV-153-Na significantly stimulates excision/synthesis repair of 8-oxoguanine (8-oxoG), abasic sites (AP sites) and alkylated bases. Laser confocal scanning fluorescence microscopy demonstrated that within the cells AV-153-Na was found mostly in the cytoplasm; however, a stain in nucleolus was also detected. Binding to cytoplasmic structures might occur due to high affinity of the compound to proteins revealed by spectroscopical methods. Discussion Activation of DNA repair enzymes after binding to DNA appears to be the basis for the antimutagenic effects of AV-153-Na.
The Aleph—Jerusalem as critical learning

This reflective paper offers the metaphor of ‘Aleph’—the ‘place of all places’—as well as the material city of Jerusalem, as points of departure for rethinking critical urban theories. In the paper, Jerusalem is ‘prized open’ as a site of learning—exposing the diversity of structural forces shaping this—and any other—city. The ‘Aleph approach’ draws attention to the relational and often changing nature in which structural forces interact as they produce urban space and society. This is highlighted by a ‘guided tour’ of Jerusalem that reveals an array of colonial, capitalist, religious, gendered and political forces of domination and their fluctuations through time and place. As such, the paper offers a ‘South-Eastern’ perspective, framed by ‘dynamic structuralism’ as foundation for new and engaged CUTs—critical urban theories. Such theories, it is suggested, should be informed by the multiple and uneven nature of oppression and resistance, and by new concepts and categories that emerge from the analysis, without treating the city as simply ‘chaotic’ or ‘self-organized’. Urban theory should move beyond the numbing theoretical dominance of ‘globalizing’ or ‘neoliberal’ capitalism, and deal seriously with simultaneous forces, movements, agents and politics that co-produce the nature of contemporary urbanism.
Diversity among 2481 Escherichia coli from women with community-acquired lower urinary tract infections in 17 countries.

OBJECTIVES In the recently published ECO.SENS survey, the antimicrobial susceptibility of Escherichia coli from urinary tract infections in women in 16 European countries and Canada was investigated. This study reports the diversity among these E. coli. METHODS The 2481 E. coli, typed with the PhenePlate (PhP) System utilizing the dynamics and end result of 11 biochemical reactions in a microplate system, were clustered and the Simpson's index of diversity calculated. RESULTS Seventy-four Common PhP Types (CT) comprising 2067 isolates and 414 Single Types (Si) were identified. Of these, 916 isolates (37%) belonged to one of the four most frequent CT (arbitrarily numbered CT48, 10, 26 and 20). CT48 with 400 isolates and 11 different susceptibility patterns, was widely disseminated across Europe and Canada and was the most frequent type in 13 countries and the second most frequent in the remaining four countries. Sixty-four per cent of the E. coli were susceptible to all eight investigated antimicrobials (CT48: 73%, CT10: 77%, CT26: 62% and CT20: 37%). Forty-six different susceptibility patterns were seen, the three most common being isolated resistance to ampicillin, resistance to ampicillin and trimethoprim, and isolated resistance to trimethoprim. Multiresistance, here defined as resistance to four or more of the investigated antibiotics, was distributed among E. coli belonging to several PhP types. CONCLUSIONS There was no obvious correlation between the phenotypes identified with the PhP System and the susceptibility pattern. The data did not indicate clonal dissemination within or between countries as a major reason for differences in antimicrobial resistance rates.
Isolation of a Variant Strain of Pleurotus eryngii and the Development of Specific DNA Markers to Identify the Variant Strain

Abstract A degenerated strain of Pleurotus eryngii KNR2312 was isolated from a commercial farm. Random amplified polymorphic DNA analysis performed on the genomic DNA of the normal and degenerated strains of this species revealed differences in the DNA banding pattern. A unique DNA fragment (1.7 kbp), which appeared only in the degenerated strain, was isolated and sequenced. Comparing this sequence with the KNR2312 genomic sequence showed that the sequence of the degenerated strain comprised three DNA regions that originated from nine distinct scaffolds of the genomic sequence, suggesting that chromosome-level changes had occurred in the degenerated strain. Using the unique sequence, three sets of PCR primers were designed that targeted the full length, the 5' half, and the 3' half of the DNA. The primer sets P2-1 and P2-2 yielded 1.76 and 0.97 kbp PCR products, respectively, only in the case of the degenerated strain, whereas P2-3 generated a 0.8 kbp product in both the normal and the degenerated strains because its target region was intact in the normal strain as well. In the case of the P2-1 and P2-2 sets, the priming regions of the forward and reverse primers were located at distinct genomic scaffolds in the normal strain. These two primer sets specifically detected the degenerate strain of KNR2312 isolated from various mushrooms including 10 different strains of P. eryngii, four strains of P. ostreatus, and 11 other wild mushrooms.
Corporate Transparency and the Impact of Investor Sentiment on Stock Prices

Using China's stock market as the testing venue, this study examines how corporate transparency helps explain the sensitivity of stock prices to general investor sentiment. We find that firms with low corporate transparency, measured by a battery of proxies including state ownership, the prevalence of related party transactions, accrual-based earnings management, audit opinions, and the quality of audit firms, are more affected by investor sentiment than are firms with high corporate transparency. Overall, our findings highlight the importance of corporate transparency in mitigating the effects of investor sentiment on stock prices. Data, as supplemental material, are available at http://dx.doi. org/10.1287/mnsc.2014. 1911. This paper was accepted by Brad Barber, finance.
A SHORT REVIEW of TPACK for TEACHER EDUCATION

The aim of this descriptive study is to examine review of the ICT and TPACK literature for teacher education. Firstly, the general characteristics of the ICT and TPACK have been examined. In the study, the researchers answer the questions namely “How is the distribution of the articles of TPACK of the year? ”, “How is the distribution of the subject of article of ICT and TPACK? ”, “What is the distribution according to the year of the subject of article of ICT and TPACK? ” and “How can we integrate the TPACK to our teacher training program? ” 116 articles were analysed. It focused on ICT and TPACK and findings and discussions were conducted. The study presents some recommendations to the teacher education. Key words: Knowledge, pedagogical knowledge, pedagogical content knowledge, technological pedagogical content knowledge, ICT.
Temporal dynamics of need satisfaction and need frustration. Two sides of the same coin?

We study the dynamics of need satisfaction and need frustration by examining how need satisfaction and need frustration change over time and how these changes relate to changes in motivation. To investigate this, volunteers were assessed daily during a delineated activity, resulting in a total sample of 77 volunteers and 467 completed daily diaries. Bayesian confirmatory factor analysis on the within-person level confirmed a bifactor solution: autonomy, competence, and relatedness were distinguished by three specific factors, but the majority of variance was explained by two strongly correlated (need satisfaction and need frustration) factors. The strong correlation between need satisfaction and need frustration further translated in the development of their relationship over time. That is, Bayesian latent growth curve modelling revealed a simultaneous, yet opposite, growth curve. Contrary to our expectations, neither of them could be related to behavioural internalization or externalization. These results imply that, at the within-person level, momentary need satisfaction and frustration are difficult to distinguish, and affecting one may automatically affect the other. Also, the relationships within the self-determination framework, such as the proposed link between need satisfaction and behavioural internalization may be better reframed with attention to the time-frame in which they occur.
Seeing Galaxies through Thick and Thin. I. Optical Opacity Measures in Overlapping Galaxies

We describe the use of partially overlapping galaxies to provide direct measurements of the effective absorption in galaxy disks, independent of assumptions about internal disk structure. The nonoverlapping parts of the galaxies and symmetry considerations are used to reconstruct, via differential photometry, how much background galaxy light is lost in passing through the foreground disks. Extensive catalog searches and follow-up imaging yield ~15-25 nearby galaxy pairs suitable for varying degrees of our analysis; 11 of the best such examples are presented here. From these pairs, we find that interarm extinction is modest, declining from AB ~ 1 mag at 0.3R to essentially zero by R; the interarm dust has a scale length consistent with that of the disk starlight. In contrast, dust in spiral arms and resonance rings may be optically thick (AB > 2) at virtually any radius. Some disks have flatter extinction curves than the Galaxy, with AB/AI ≈ 1.6; this is probably the signature of clumpy dust distributions. Even though typical spirals are not optically thick throughout their disks, where they are optically thick is correlated with where they are most luminous: in spiral arms and inner disks. This correlation between absorption and emission regions may account for their apparent surface brightness being only mildly dependent on inclination, erroneously indicating that spirals are generally optically thick. Taken as an ensemble, the opacities of spiral galaxies may be just great enough to significantly affect QSO counts, though not enough to cause their high-redshift cutoff.
Incidence of metastasis and prostate-specific antigen levels at diagnosis in Gleason 3+4 versus 4+3 prostate cancer

Aims: The aim is to assess for a difference in the incidence of metastasis (IM) and prostate-specific antigen (PSA) levels at diagnosis in patients with Gleason score (GS) 3+4 versus 4+3 prostate cancer using a large veterans affairs database. Subjects and Methods: A retrospective review of 1402 medical records from 5 VA hospitals was conducted. The study period was from 2009 to 2014. Primary endpoints were IM and PSA levels at diagnosis. A secondary endpoint was overall survival. Statistical Analysis Used: Chi-square tests for categorical variables, Student's t-test for continuous, normally distributed variables, and rank sum tests for continuous nonnormally distributed variables. Results: There were 1050 patients with GS3+4 and 352 with GS4+3. There were no differences in sociodemographic and clinical characteristics of the study population. PSA at the time of diagnosis was significantly higher in the GS4+3 patients compared to GS3+4 (18.0 vs. 11.4, respectively; P < 0.001). The IM at diagnosis was higher in the GS4+3 patients (10/352) compared to GS3+4 (9/1041) (2.8% vs. 0.9%; P = 0.005). In an adjusted model, GS4+3 was associated with higher PSA, higher IM at diagnosis. There was no difference in overall survival between the 2 groups though a 23% reduction in overall survival in the GS4+3 was noted (P = 0.53). Conclusions: Our results indicate that patients with GS4+3 prostate cancers have higher PSA levels at diagnosis. GS4+3 is associated with 3-fold increased risk of IM at diagnosis than GS3+4 though the overall incidence is low. Further research is needed to assess whether GS4+3 patients need routine staging imaging investigations at the time of diagnosis similar to patients with higher Gleason scores (GS ≥8).
Not all effort is equal: the role of the anterior cingulate cortex in different forms of effort-reward decisions

The rat anterior cingulate cortex (ACC) mediates effort-based decision making when the task requires the physical effort of climbing a ramp. Normal rats will readily climb a barrier leading to high reward whereas rats with ACC lesions will opt instead for an easily obtained small reward. The present study explored whether the role of ACC in cost-benefit decisions extends beyond climbing by testing its role in ramp climbing as well as two novel cost-benefit decision tasks, one involving the physical effort of lifting weights and the other the emotional cost of overcoming fear (i.e., “courage”). As expected, rats with extensive ACC lesions tested on a ramp-climbing task were less likely to choose a high-reward/high-effort arm than sham controls. However, during the first few trials, lesioned rats were as likely as controls to initially turn into the high-reward arm (HRA) but far less likely to actually climb the barrier, suggesting that the role of the ACC is not in deciding which course of action to pursue, but rather in maintaining a course of action in the face of countervailing forces. In the effort-reward decision task involving weight lifting, some lesion animals behaved like controls while others avoided the HRA. However, the results were not statistically significant and a follow-up study using incremental increasing effort failed to show any difference between lesion and control groups. The results suggest that the ACC is not needed for effort-reward decisions involving weight lifting but may affect motor abilities. Finally, a courage task explored the willingness of rats to overcome the fear of crossing an open, exposed arm to obtain a high reward. Both sham and ACC-lesioned animals exhibited equal tendencies to enter the open arm. However, whereas sham animals gradually improved on the task, ACC-lesioned rats did not. Taken together, the results suggest that the role of the ACC in effort-reward decisions may be limited to certain tasks.