Transcription enhancement of a digitised multi-lingual pamphlet collection: a case study and guide for similar projects

UCL Library Services holds an extensive collection of over 9,000 Jewish pamphlets, many of these extremely rare. Over the past five years, UCL has embarked on a project to widen access to this collection through an extensive programme of cataloguing, conservation and digitisation. With the cataloguing complete and the most fragile items conserved, the focus is now on making these texts available to global audiences via UCL Digital Collections website. The pamphlets were ranked for rarity, significance and fragility and the highest-scoring selected for digitisation. Unique identifiers allocated at the point of cataloguing were used to track individual pamphlets through the stages of the project. This guide details the text-enhancement methods used, highlighting particular issues relating to Hebrew scripts and early-printed texts. Initial attempts to enable images of these pamphlets to be searched digitally relied on the Optical Character Recognition (OCR) embedded within the software used to create the PDF files. Whilst satisfactory for texts chiefly in Roman script, it provided no reliable means to search the extensive corpus of texts in Hebrew. Generous advice offered by the National Library of Israel led to our adoption of ABBYY FineReader software as a means of enhancing the transcriptions embedded within the PDF files. Following image capture, JPEG files were used to create multi-page PDF files of each pamphlet. Pre-processing in ABBYY FineReader consisted of: setting the language and colour mode; detecting page orientation; selecting and refining areas of the text to be read; reading the text to produce a transcription. The resultant files were stored in folders according to language of text. The software highlighted spelling errors and doubtful readings. A verification tool allowed transcribers to correct these as required. However, some erroneous or doubtful readings were nevertheless genuine words and not highlighted; it was therefore essential to proofread the text, particularly for early-printed scripts. Transcribers maintained logs of common errors; additionally, problems with Hebrew vocalisations, cursive and Gothic scripts were noted. During initial quality checks of the transcriptions, many text searches were unsuccessful due to previously unidentified spacings occurring within words. This was generally linked to the font size being too small. Maintaining logs of font sizes used led to the adoption of a minimum of Arial 8 or Times New Roman 10 in transcribed text. The methodology was revised to include the preliminary quality-checking of one page. We concluded that it was difficult to develop a standardised procedure applicable to all texts given the variance in language, script and typography. However, we concluded that the font Arial gave the most successful accuracy ratings for Hebrew script, minimum text size 17, minimum title size 25. ABBYY file preparation took a minimum of 1.5 hours per pamphlet; transcription correction took an average of 10.4 minutes per page; the final quality check took 30 minutes per pamphlet. On average, the work on each pamphlet took a minimum of 6 hours to complete. As a result of the project, average accuracy ratings improved from 60% to 89%, the greatest improvement being for pre-1800 and Hebrew script publications. We are therefore inclined to focus future transcription-enhancement activity on these types of publication for the remainder of our Jewish Pamphlet Collections

Physics-Based Deep Learning for Imaging Neuronal Activity via Two-Photon and Light Field Microscopy

Light Field Microscopy (LFM) is an imaging technique that offers the opportunity to study fast dynamics in biological systems due to its 3D imaging speed and is particularly attractive for functional neuroimaging. Traditional model-based approaches employed in microscopy for reconstructing 3D images from light-field data are affected by reconstruction artifacts and are computationally demanding. This work introduces a deep neural network for LFM to image neuronal activity under adverse conditions: limited training data, background noise, and scattering mammalian brain tissue. The architecture of the network is obtained by unfolding the ISTA algorithm and is based on the observation that neurons in the tissue are sparse. Our approach is also based on a novel modelling of the imaging system that uses a linear convolutional neural network to fit the physics of the acquisition process. We train the network in a semi-supervised manner based on an adversarial training framework. The small labelled dataset required for training is acquired from a single sample via two-photon microscopy, a point-scanning 3D imaging technique that achieves high spatial resolution and deep tissue penetration but at a lower speed than LFM. We introduce physics knowledge of the system in the design of the network architecture and during training to complete our semi-supervised approach. We experimentally show that in the proposed scenario, our method performs better than typical deep learning and model-based reconstruction strategies for imaging neuronal activity in mammalian brain tissue via LFM, considering reconstruction quality, generalization to functional imaging, and reconstruction speed

Psychosocial adversity and socioeconomic position during childhood and epigenetic age: analysis of two prospective cohort studies

Psychosocial adversity in childhood (e.g. abuse) and low socioeconomic position (SEP) can have significant lasting effects on social and health outcomes. DNA methylation-based biomarkers are highly correlated with chronological age; departures of methylation-predicted age from chronological age can be used to define a measure of age acceleration, which may represent a potential biological mechanism linking environmental exposures to later health outcomes. Using data from two cohorts of women Avon Longitudinal Study of Parents and Children, (ALSPAC), N = 989 and MRC National Survey of Health and Development, NSHD, N = 773), we assessed associations of SEP, psychosocial adversity in childhood (parental physical or mental illness or death, parental separation, parental absence, sub-optimal maternal bonding, sexual, emotional and physical abuse and neglect) and a cumulative score of these psychosocial adversity measures, with DNA methylation age acceleration in adulthood (measured in peripheral blood at mean chronological ages 29 and 47 in ALSPAC and buccal cells at age 53 in NSHD). Sexual abuse was strongly associated with age acceleration in ALSPAC (sexual abuse data were not available in NSHD), e.g. at the 47-year time point sexual abuse associated with a 3.41 years higher DNA methylation age (95% CI 1.53 to 5.29) after adjusting for childhood and adulthood SEP. No associations were observed between low SEP, any other psychosocial adversity measure or the cumulative psychosocial adversity score and age acceleration. DNA methylation age acceleration is associated with sexual abuse, suggesting a potential mechanism linking sexual abuse with adverse outcomes. Replication studies with larger sample sizes are warranted

Lentiviral vectors can be used for full-length dystrophin gene therapy

Duchenne Muscular Dystrophy (DMD) is caused by a lack of dystrophin expression in patient muscle fibres. Current DMD gene therapy strategies rely on the expression of internally deleted forms of dystrophin, missing important functional domains. Viral gene transfer of full-length dystrophin could restore wild-type functionality, although this approach is restricted by the limited capacity of recombinant viral vectors. Lentiviral vectors can package larger transgenes than adeno-associated viruses, yet lentiviral vectors remain largely unexplored for full-length dystrophin delivery. In our work, we have demonstrated that lentiviral vectors can package and deliver inserts of a similar size to dystrophin. We report a novel approach for delivering large transgenes in lentiviruses, in which we demonstrate proof-of-concept for a 'template-switching' lentiviral vector that harnesses recombination events during reverse-transcription. During this work, we discovered that a standard, unmodified lentiviral vector was efficient in delivering full-length dystrophin to target cells, within a total genomic load of more than 15,000 base pairs. We have demonstrated gene therapy with this vector by restoring dystrophin expression in DMD myoblasts, where dystrophin was expressed at the sarcolemma of myotubes after myogenic differentiation. Ultimately, our work demonstrates proof-of-concept that lentiviruses can be used for permanent full-length dystrophin gene therapy, which presents a significant advancement in developing an effective treatment for DMD

Shift-invariant-subspace discretization and volume reconstruction for light field microscopy

Light Field Microscopy (LFM) is an imaging technique that captures 3D spatial information with a single 2D image. LFM is attractive because of its relatively simple implementation and fast volume acquisition rate. Capturing volume time series at a camera frame rate can enable the study of the behaviour of many biological systems. For instance, it could provide insights into the communication dynamics of living 3D neural networks. However, conventional 3D reconstruction algorithms for LFM typically suffer from high computational cost, low lateral resolution, and reconstruction artifacts. In this work, we study the origin of these issues and propose novel techniques to improve the performance of the reconstruction process. First, we propose a discretization approach that uses shift-invariant subspaces to generalize the typical discretization framework used in LFM. Then, we study the shift-invariant-subspace assumption as a prior for volume reconstruction under ideal conditions. Furthermore, we present a method to reduce the computational time of the forward model by using singular value decomposition (SVD). Finally, we propose to use iterative approaches that incorporate additional priors to perform artifact-free 3D reconstruction from real light field images. We experimentally show that our approach performs better than Richardson-Lucy-based strategies in computational time, image quality, and artifact reduction

Iron homeostasis and oxidative stress in idiopathic pulmonary alveolar proteinosis: a case-control study

<p>Abstract</p> <p>Background</p> <p>Lung injury caused by both inhaled dusts and infectious agents depends on increased availability of iron and metal-catalyzed oxidative stress. Because inhaled particles, such as silica, and certain infections can cause secondary pulmonary alveolar proteinosis (PAP), we tested the hypothesis that idiopathic PAP is associated with an altered iron homeostasis in the human lung.</p> <p>Methods</p> <p>Healthy volunteers (n = 20) and patients with idiopathic PAP (n = 20) underwent bronchoalveolar lavage and measurements were made of total protein, iron, tranferrin, transferrin receptor, lactoferrin, and ferritin. Histochemical staining for iron and ferritin was done in the cell pellets from control subjects and PAP patients, and in lung specimens of patients without cardiopulmonary disease and with PAP. Lavage concentrations of urate, glutathione, and ascorbate were also measured as indices of oxidative stress.</p> <p>Results</p> <p>Lavage concentrations of iron, transferrin, transferrin receptor, lactoferrin, and ferritin were significantly elevated in PAP patients relative to healthy volunteers. The cells of PAP patients had accumulated significant iron and ferritin, as well as considerable amounts of extracellular ferritin. Immunohistochemistry for ferritin in lung tissue revealed comparable amounts of this metal-storage protein in the lower respiratory tract of PAP patients both intracellularly and extracellularly. Lavage concentrations of ascorbate, glutathione, and urate were significantly lower in the lavage fluid of the PAP patients.</p> <p>Conclusion</p> <p>Iron homeostasis is altered in the lungs of patients with idiopathic PAP, as large amounts of catalytically-active iron and low molecular weight anti-oxidant depletion are present. These findings suggest a metal-catalyzed oxidative stress in the maintenance of this disease.</p

Privacy in crowdsourcing:a systematic review

The advent of crowdsourcing has brought with it multiple privacy challenges. For example, essential monitoring activities, while necessary and unavoidable, also potentially compromise contributor privacy. We conducted an extensive literature review of the research related to the privacy aspects of crowdsourcing. Our investigation revealed interesting gender differences and also differences in terms of individual perceptions. We conclude by suggesting a number of future research directions.</p

Enteric Neurospheres Are Not Specific to Neural Crest Cultures: Implications for Neural Stem Cell Therapies

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited

Envelope Determinants of Equine Lentiviral Vaccine Protection

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. © 2013 Craigo et al

Assessment of the direct effects of DDAH I on tumour angiogenesis in vivo

Nitric oxide (NO) has been strongly implicated in glioma progression and angiogenesis. The endogenous inhibitors of NO synthesis, asymmetric dimethylarginine (ADMA) and N-monomethyl-l-arginine (l-NMMA), are metabolized by dimethylarginine dimethylaminohydrolase (DDAH), and hence, DDAH is an intracellular factor that regulates NO. However, DDAH may also have an NO-independent action. We aimed to investigate whether DDAH I has any direct role in tumour vascular development and growth independent of its NO-mediated effects, in order to establish the future potential of DDAH inhibition as an anti-angiogenic treatment strategy. A clone of rat C6 glioma cells deficient in NO production expressing a pTet Off regulatable element was identified and engineered to overexpress DDAH I in the absence of doxycycline. Xenografts derived from these cells were propagated in the presence or absence of doxycycline and susceptibility magnetic resonance imaging used to assess functional vasculature in vivo. Pathological correlates of tumour vascular density, maturation and function were also sought. In the absence of doxycycline, tumours exhibited high DDAH I expression and activity, which was suppressed in its presence. However, overexpression of DDAH I had no measurable effect on tumour growth, vessel density, function or maturation. These data suggest that in C6 gliomas DDAH has no NO-independent effects on tumour growth and angiogenesis, and that the therapeutic potential of targeting DDAH in gliomas should only be considered in the context of NO regulation