Miracle-dz/UniFAR-FTUs huggingface dataset:
The cell cycle effects and induction of apoptosis by 5‐bromouridine in cultures of human leukaemic MOLT‐4 and HL‐60 cell lines and mitogen‐stimulated normal lymphocytes

Abstract. 5‐Bromouridine (BrUrd) and several analogues of this antimetabolite exhibit antiviral activity and are potent inhibitors of the human immunodeficiency virus. The antitumour activity of BrUrd, however, in comparison with 5‐fluorouridine or 5‐fluorouracil, is less pronounced. Because BrUrd is incorporated into RNA and can be detected immunocytochemically and analysed by cytometry, it may prove useful as an RNA precursor to assay cell transcriptional activity. The aim of the present study was to evaluate the cell cycle effects of BrUrd incorporation in human lymphocytic leukaemic MOLT‐4 and HL‐60 cells and mitogenically stimulated normal peripheral blood lymphocytes. BrUrd suppressed cell proliferation and induced cell death; when measured after 72 h of treatment, the LD50 was 10 and 20μm for HL‐60 and MOLT‐4, respectively, and LD90 was 100μm, for both cell lines. BrUrd was maximally incorporated by the cells progressing through S phase of the cycle and the S phase cells were most severely perturbed by the drug, which was detected in RNA but not in DNA. Suppression of the S phase traverse of MOLT‐4, HL‐60 and normal lymphocytes was seen at ≫30μm BrUrd concentration. Also sensitive was the cell traverse through G2+M which, in the case of lymphocytes, HL‐60 and MOLT‐4 cells, was perturbed at ≫30, ≫200 and 500μm BrUrd concentrations, respectively. Transition of lymphocytes from G0 to G1 was little affected at <100μm, and, although suppressed, was still observed even at 500μm BrUrd concentration. Apoptosis of HL‐60 cells and lymphocytes was observed at ≫50μm BrUrd after 24 h of incubation; death of MOLT‐4 cells had mixed features of apoptosis and necrosis and resembled the ‘mitotic’ or ‘reproductive cell death‘ as described in other cell systems. The cytostatic and cytotoxic effects of BrUrd should be taken into consideration when using this antimetabolite as an antiviral agent in the clinic or as an RNA precursor in assays of cell transcriptional activity.
The role of Epstein–Barr virus in cancer

Epstein–Barr virus (EBV), discovered > 40 years ago from a Burkitt’s lymphoma biopsy, was the first virus to be directly associated with human cancer. EBV has two distinct life cycles in the human host; a lytic form of infection that produces new infectious virions, and a latent form of infection that allows the virus to persist in a dormant state for the lifetime of the host. EBV has evolved a life cycle that mimics the natural differentiation pathway of antigen-activated B cells, giving the virus access to its site of latent infection, the resting memory B cell. By steering infected cells through the various stages of lymphocyte differentiation, EBV is able to enter a cell type suitable for long-term latent persistence and periodic reactivation. However, its presence in various stages of B-cell development, and its ability to infect certain epithelial cells, can have pathogenic consequences, and can contribute to the development of a diverse group of lymphomas and carcinomas. The presence of EBV in the tumour cells of EBV-associated cancers might provide a basis for specific therapy. This article focuses on the contributions that the virus may play in different types of human cancer, particularly Burkitt’s lymphoma, Hodgkin’s lymphoma, lymphomas and lymphoproliferative diseases in the immunocompromised, and nasopharyngeal and gastric carcinoma.
Towards a Methodology for Engineering Self-Organising Emergent Systems

When designing self-organising emergent multi-agent systems (MASs), a fundamental engineering issue is to achieve a macroscopic behaviour that meets the requirements and emerges only from the behaviour of locally interacting agents. Agent-oriented methodologies today are mainly focussed on engineering the microscopic issues, i.e. the agents, their rules, how they interact, etc, without explicit support for engineering the required macroscopic behaviour. As a consequence, the macroscopic behaviour is achieved in an ad-hoc manner. This paper proposes a way to define a full life-cycle methodology based on an industry-ready software engineering process, i.e. the Unified Process, which is customised to explicitly focus on engineering macroscopic behaviour of self-organising emergent MASs. As such, the MAS paradigm is integrated into an existing and widely accepted methodology and we can systematically develop a solution that exhibits the required macroscopic behaviour.
Research into the pathogenesis of keratoconus. A new syndrome: low ocular rigidity, contact lenses, and keratoconus.

Ocular rigidity determinations were carried out in three groups of patients who were successful long-term wearers of corneal contact lenses. Group 1 consisted of those patients whose corneas showed no refractive changes upon removal of the lenses (as compared to their precontact refraction). Group 2 were patients who had developed permanent with-the-rule astigmatism. Group 3 were patients who developed keratoconus. Though our series is too small for statistical analysis, it would appear that at least one type of keratoconus may be related to the long-term wearing of corneal contact lenses on eyes that have an unusually low ocular rigidity.
Fuzzy optimization for a batch simultaneous saccharification and co-fermentation process by hybrid differential evolution

The crisp and fuzzy optimization approaches were introduced to design an optimal temperature control policy for a batch process of simultaneous saccharification and cofermentation (SSCF) to produce ethanol from lignocellulose using the enzymes and the recombinant strain Saccharomyces yeast 1400 (pLNH33). The goal of the optimal design herein is to find the optimal temperature, initial lignocellulosic concentration, and fermentation time that maximize the ethanol productivity under the constraints of follow-up separation specifications. The interactive crisp and fuzzy optimization methods towards were respectively applied to solve the trade-off optimization problems in order to obtain a compromised design. The fuzzy goal attainment approach can more flexibly obtain a comprehensive design in comparison to the crisp optimization. Both crisp and fuzzy optimization could be efficiently solved by hybrid differential evolution.
Envelope enhancement for improving hearing in reverberant spaces

Cochlear implants are neural prostheses which give a sense of hearing to deaf people by stimulating the auditory nerve. In many users they restore the ability to understand speech in quiet, but noise and reverberation cause severe problems. It seems that implant users have difficulties hearing out one source in a potpourri of sources. This so called “auditory scene analysis” relies, amongst other cues, on binaural information which is degraded with implants. Sound localization ability, directly dependent on access to binaural cues, is highly sensitive to the presence of noise or reverberation [1, 2]. These studies have shown that noise and reverberation affects localization ability of cochlear implant users already at a signal-to-noise ratio (or direct-to-reverberant ratio) about 6-12 dB more positive than that found with normal hearing listeners. Here we focus on the coding of binaural information to improve the perception of sound direction – an important aspect for locating and understanding speakers. Several ways exist to improve the coding of binaural cues in reverberation in cochlear implants. Most past approaches have attempted to reduce the energy of the interfering reverberation or noise. Our novel approach instead aims to increase the perceptual saliency of the cues used to locate sounds in reverberation. Studies of sound localization and the precedence effect have shown that information in the sound onset is important for correct localization in reverberant space [3, 4, 5, 6]. Onset information is transmitted in the modulated envelope of the electrode signals in cochlear implants. However, due to the bandbass filtering and compression stages in the implant, modulation depth and onset gradient inherent in envelope fluctuations are reduced – both are important factors for transmitting interaural time difference cues (ITDs) in the envelope [3].
Adaptive seating systems in children with severe cerebral palsy across International Classification of Functioning, Disability and Health for Children and Youth version domains: a systematic review

The aim of this study was to systematically review the effect of adaptive seating systems (AdSSs) in young people less than 19 years of age with severe cerebral palsy (CP), with particular focus on child‐related outcomes across all components of the functioning and disability domains of the International Classification of Functioning, Disability, and Health for Children and Youth version (ICF‐CY).
Escherichia coli O157:H7 Colonization in Cattle following Systemic and Mucosal Immunization with Purified H7 Flagellin

ABSTRACT Escherichia coli O157:H7 is an important pathogen of humans. Cattle are most frequently identified as the primary source of infection, and therefore, reduction in E. coli O157:H7 prevalence in cattle by vaccination represents an attractive strategy for reducing the incidence of human disease. H7 flagella have been implicated in intestinal-epithelial colonization of E. coli O157:H7 and may represent a useful target for vaccination. In this study, calves were immunized either systemically with H7 flagellin by intramuscular injection or mucosally via the rectum with either H7 or H7 incorporated into poly(dl-lactide-co-glycolide) microparticles (PLG:H7). Systemic immunization resulted in high levels of flagellin-specific immunoglobulin G (IgG) and IgA in both serum and nasal secretions and detectable levels of both antibody isotypes in rectal secretions. Rectal administration of flagellin resulted in levels of rectal IgA similar to those by the intramuscular route but failed to induce any other antibody response, whereas rectal immunization with PLG:H7 failed to induce any H7-specific antibodies. Following subsequent oral challenge with E. coli O157:H7, reduced colonization rates and delayed peak bacterial shedding were observed in the intramuscularly immunized group compared to nonvaccinated calves, but no reduction in total bacterial shedding occurred. Rectal immunization with either H7 or PLG:H7 had no effect on subsequent bacterial colonization or shedding. Furthermore, purified H7-specific IgA and IgG from intramuscularly immunized calves were shown to reduce intestinal-epithelial binding in vitro. These results indicate that H7 flagellin may be a useful component in a systemic vaccine to reduce E. coli O157:H7 colonization in cattle.
Treatment Results Of Spiral and Oblique Distal One-Third Tibia-Fibula Fractures With Interlocking Nails and Poller Screw

Distal tibia fibula fracture near ankle joint is difficult to manage. Because of poor soft tissue coverage and blood supply these fractures often goes in nonunion and soft tissue problems. This study is to evaluate clinical outcome in distal tibia fibula fracture treated with interlocking nail and supplemented with poller screw. Material And Methods 34 patients with spiral and oblique fractures of distal tibia fibula within 4 cm of ankle joint were treated with intramedullary nail with supplementary poller screw between March 2012 and Febuarury 2014 with minimum follow up of fifteen months. The type of fractures based on AO classificationA1 (n=14), A2 (n=5), A3 (n=9), B1 (n=4), and C1 (n=2). Results And Conclusions All fractures united with a mean union time of 14.7±3.21 weeks. Results were evaluated for angulation, shortness and ankle function . Using Iowa score outcome was excellent to good in 88% cases. No major complication occurred. We conclude that tibia interlocking nailing along with poller screw is reliable method for distal tibia fibula fracture, with this technique there is less complication such as shortening or angulation, better stability and early mobilization can be
The First-passage Time of the Brownian Motion to a Curved Boundary: an Algorithmic Approach

Under some weak conditions, the first-passage time of the Brownian motion to a continuous curved boundary is an almost surely finite stopping time. Its probability density function (pdf) is explicitly known only in few particular cases. Several mathematical studies proposed to approximate the pdf in a quite general framework or even to simulate this hitting time using a discrete time approximation of the Brownian motion. The authors study a new algorithm which permits to simulate the first-passage time using an iterating procedure. The convergence rate presented in this paper suggests that the method is very efficient.
Maternal smoking does not affect fetal size as measured in the mid‐second trimester

Background. Cigarette smoking during pregnancy is causally related to birthweight, but we do not know whether fetal growth restriction is a continuous process or, if not, at what stage of pregnancy it affects weight gain. Material and methods. A random sample of para 1 and 2 mothers, drawn from the population of pregnant women in Bergen and Trondheim, Norway, and Uppsala, Sweden, were examined by a detailed questionnaire concerning smoking habits, menstrual history and pregnancy dating, and subjected to morphometric sonography of their fetuses in or around week 17. Of the 547 study participants, 31.9% were smokers. Gestational age was primarily determined by the last menstrual period [LMP], except in those with irregular cycles, and in 30 cases (6.6% of those with regular cycles) in whom the biparietal diameter [BPD]‐determined age deviated >14 days from the LMP‐based date. Results. The analysis did not reveal any statistically significant differences between the fetuses of non‐smokers, light smokers (0–9 cigarettes per day) and heavy (10+ cigarettes per day) smokers, regarding BPD, mean abdominal diameter [MAD] femur length [FL], and a ‘body contour index’: [BPD+FL]÷MAD. Conclusion. Tobacco‐induced fetal growth restriction probably begins after gestational week 17.
Synthesis and Characterization of Optically Active Poly(amide-imide)s with Hydantoin and Thiohydantoin Derivatives in the Main Chain

Hydantoin and thiohydantoin derivatives 4(a-e) were synthesized from reactions of benzil and benzil derivatives 3(a-e) with urea and thiourea. 5,5-dimethylhydantoin 4f was synthesized from the reactions of acetone cyanohydrin 3f and ammonium carbonate. Benzil and benzil derivatives 3(a-e) were obtained from oxidation of benzoin and benzoin derivatives 2(a-e) with concentrated nitric acid. Benzoin and benzoin derivatives were obtained from benzoin condensation of benzaldehyde and benzaldehyde derivatives. Hydantoin and thiohydantoin derivatives 4(a-e) were characterized by melting points, elemental analysis, FTIR, H NMR and C NMR spectroscopy. The polycondensation reactions of 4,4-carbonyl-bis(phthaloyl-L-alanine) diacid chloride 5 with six different derivatives of hydantoin and thiohydantoin compounds 4(a-f) were carried out in DMAc solution in the presence of pyridine. The resulting poly(amide-imide)s, PAIs, 6(a-f) with inherent viscosities about 0.15-0.38 dL/g were obtained in high yield and were optically active and thermally stable. All of the above compounds were fully characterized by means of FTIR spectroscopy, elemental analysis, inherent viscosity (ηinh), solubility test and specific rotation. Thermal properties of the PAIs 6(a-f) were investigated using thermal gravimetric analysis (TGA). Khalil Faghihi*, Khosrow Zamani and Shadpour Mallakpour (1) Department of Chemistry, Arak University, Arak 38156, I.R. Iran (2) Organic Polymer Chemistry Research Laboratory, College of Chemistry, Isfahan University of Technology, Isfahan 84156, I.R. Iran
Iterative inversion of neural networks and its application to adaptive control

An iterative constrained inversion technique is used to find the control inputs to the plant. That is, rather than training a controller network and placing this network directly in the feedback or feedforward paths, the forward model of the plant is learned, and iterative inversion is performed on line to generate control commands. The control approach allows the controllers to respond online to changes in the plant dynamics. This approach also attempts to avoid the difficulty of analysis introduced by most current neural network controllers, which place the highly nonlinear neural network directly in the feedback path. A neural network-based model reference adaptive controller is also proposed for systems having significant dynamics between the control inputs and the observed (or desired) outputs and is demonstrated on a simple linear control system. These results are interpreted in terms of the need for a dither signal for on-line identification of dynamic systems.
Performance of Healthy, Older Adults on the Tower of London Revised: Associations with Verbal and Nonverbal Abilities

ABSTRACT Neuropsychological studies suggest a subclinical impairment in executive function that occurs with normal aging. This is the first study to examine the performance of healthy older adults on the Tower of London-Revised (TOL-R), as well as the relationship between TOL-R performance and verbal and nonverbal abilities. Performance of 63 older adult participants on the TOL-R and two WAIS-III subtests was compared to that of 35 young adult college students. Group comparisons indicated age differences in TOL-R performance; however, these were eliminated after adjusting for individual differences in Matrix Reasoning performance. In the older adult groups, multiple regression analyses demonstrated that Matrix Reasoning performance was a stronger predictor of TOL-R performance than was chronological age or years of education. These results suggest that performance on the TOL-R is a psychometrically sound executive function measure for older adults and that individual differences in fluid intelligence are more predictive of performance than chronological age.
Blood-based profiles of DNA methylation predict the underlying distribution of cell types

The potential influence of underlying differences in relative leukocyte distributions in studies involving blood-based profiling of DNA methylation is well recognized and has prompted development of a set of statistical methods for inferring changes in the distribution of white blood cells using DNA methylation signatures. However, the extent to which this methodology can accurately predict cell-type proportions based on blood-derived DNA methylation data in a large-scale epigenome-wide association study (EWAS) has yet to be examined. We used publicly available data deposited in the Gene Expression Omnibus (GEO) database (accession number GSE37008), which consisted of both blood-derived epigenome-wide DNA methylation data assayed using the Illumina Infinium HumanMethylation27 BeadArray and complete blood cell (CBC) counts among a community cohort of 94 non-diseased individuals. Constrained projection (CP) was used to obtain predictions of the proportions of lymphocytes, monocytes and granulocytes for each of the study samples based on their DNA methylation signatures. Our findings demonstrated high consistency between the average CBC-derived and predicted percentage of monocytes and lymphocytes (17.9% and 17.6% for monocytes and 82.1% and 81.4% for lymphocytes), with root mean squared error (rMSE) of 5% and 6%, for monocytes and lymphocytes, respectively. Similarly, there was moderate-high correlation between the CP-predicted and CBC-derived percentages of monocytes and lymphocytes (0.60 and 0.61, respectively), and these results were robust to the number of leukocyte differentially methylated regions (L-DMRs) used for CP prediction. These results serve as further validation of the CP approach and highlight the promise of this technique for EWAS where DNA methylation is profiled using whole-blood genomic DNA.
Characterization of the interactions of human ZIC3 mutants with GLI3

ZIC3, a GLI superfamily transcription factor, is involved in establishing normal embryonic left–right patterning. Multiple abnormalities in the central nervous system (CNS) and axial skeleton have also been observed in mice bearing a Zic3 null allele, mice with a Zic3 overexpression allele, and the majority of patients carrying ZIC3 mutations. Previous studies indicate that ZIC3 protein can bind to the GLI consensus binding site (GLIBS) and physically interact with GLI3, a transcription factor involved in multiple aspects of neural and skeletal development. We investigated in vitro interactions of ZIC3 with GLI3 and the effect of ZIC3 mutations identified in patients with either heterotaxy or isolated cardiovascular malformations. Electrophoresis mobility shift assay (EMSA) revealed that all five intact zinc finger (ZF) domains were necessary for binding of ZIC3 to GLIBS. Inclusion of GLIBS upstream of a basal TK promoter had no effect on the activation of the promoter by ZIC3 alone, but it enhanced the synergistic activation of ZIC3 and GLI3. Wild‐type (WT) ZIC3 showed specific binding to GLI3 in GST‐pull‐down assays. Nonsense and frameshift ZIC3 mutants lacking one or more of the zinc finger domains did not physically interact with GST‐GLI3; however, two missense mutants c.1213A>G (p.K405E, fifth ZF domain), and c.649C>G (p.P217A, conserved N‐terminal domain) retained binding. Luciferase reporter assays indicated that both p.P217A and p.K405E mutants also retained coactivation with GLI3 of reporter gene expression activity, while all the GLI3‐nonbinding ZIC3 mutants lacked this activity. Interestingly, no CNS or skeletal abnormalities were observed in patients bearing the p.P217A or p.K405E mutations. Hum Mutat 29(1), 99–105, 2008. Published 2007 Wiley‐Liss, Inc.
Data point selection for genre-aware parsing

In the NLP literature, adapting a parser to new text with properties different from the training data is commonly referred to as domain adaptation. In practice, however, the differences between texts from different sources often reflect a mixture of domain and genre properties, and it is by no means clear what impact each of those has on statistical parsing. In this paper, we investigate how differences between articles in a newspaper corpus relate to the concepts of genre and domain and how they influence parsing performance of a transition-based dependency parser. We do this by applying various similarity measures for data point selection and testing their adequacy for creating genre-aware parsing models.