Miracle-dz/UniFAR-FTUs huggingface dataset:
The 1.7 Å X-Ray Crystal Structure of the Porcine Factor VIII C2 Domain and Binding Analysis to Anti-Human C2 Domain Antibodies and Phospholipid Surfaces

The factor VIII C2 domain is essential for binding to activated platelet surfaces as well as the cofactor activity of factor VIII in blood coagulation. Inhibitory antibodies against the C2 domain commonly develop following factor VIII replacement therapy for hemophilia A patients, or they may spontaneously arise in cases of acquired hemophilia. Porcine factor VIII is an effective therapeutic for hemophilia patients with inhibitor due to its low cross-reactivity; however, the molecular basis for this behavior is poorly understood. In this study, the X-ray crystal structure of the porcine factor VIII C2 domain was determined, and superposition of the human and porcine C2 domains demonstrates that most surface-exposed differences cluster on the face harboring the “non-classical” antibody epitopes. Furthermore, antibody-binding results illustrate that the “classical” 3E6 antibody can bind both the human and porcine C2 domains, although the inhibitory titer to human factor VIII is 41 Bethesda Units (BU)/mg IgG versus 0.8 BU/mg IgG to porcine factor VIII, while the non-classical G99 antibody does not bind to the porcine C2 domain nor inhibit porcine factor VIII activity. Further structural analysis of differences between the electrostatic surface potentials suggest that the C2 domain binds to the negatively charged phospholipid surfaces of activated platelets primarily through the 3E6 epitope region. In contrast, the G99 face, which contains residue 2227, should be distal to the membrane surface. Phospholipid binding assays indicate that both porcine and human factor VIII C2 domains bind with comparable affinities, and the human K2227A and K2227E mutants bind to phospholipid surfaces with similar affinities as well. Lastly, the G99 IgG bound to PS-immobilized factor VIII C2 domain with an apparent dissociation constant of 15.5 nM, whereas 3E6 antibody binding to PS-bound C2 domain was not observed.
Antibodies VRC01 and 10E8 Neutralize HIV-1 with High Breadth and Potency Even with Ig-Framework Regions Substantially Reverted to Germline

Abs capable of effectively neutralizing HIV-1 generally exhibit very high levels of somatic hypermutation, both in their CDR and framework-variable regions. In many cases, full reversion of the Ab-framework mutations back to germline results in substantial to complete loss of HIV-1–neutralizing activity. However, it has been unclear whether all or most of the observed framework mutations would be necessary or whether a small subset of these mutations might be sufficient for broad and potent neutralization. To address this issue and to explore the dependence of neutralization activity on the level of somatic hypermutation in the Ab framework, we applied a computationally guided framework-reversion procedure to two broadly neutralizing anti–HIV-1 Abs, VRC01 and 10E8, which target two different HIV-1 sites of vulnerability. Ab variants in which up to 78% (38 of 49 for VRC01) and 89% (31 of 35 for 10E8) of framework mutations were reverted to germline retained breadth and potency within 3-fold of the mature Abs when evaluated on a panel of 21 diverse viral strains. Further, a VRC01 variant with an ∼50% framework-reverted L chain showed a 2-fold improvement in potency over the mature Ab. Our results indicate that only a small number of Ab-framework mutations may be sufficient for high breadth and potency of HIV-1 neutralization by Abs VRC01 and 10E8. Partial framework revertants of HIV-1 broadly neutralizing Abs may present advantages over their highly mutated counterparts as Ab therapeutics and as targets for immunogen design.
Steps in Moving Evidence-Based Health Informatics from Theory to Practice

Objectives To demonstrate and promote the importance of applying a scientific process to health IT design and implementation, and of basing this on research principles and techniques. Methods A review by international experts linked to the IMIA Working Group on Technology Assessment and Quality Development. Results Four approaches are presented, linking to the creation of national professional expectations, adherence to research-based standards, quality assurance approaches to ensure safety, and scientific measurement of impact. Conclusions Solely marketing- and aspiration-based approaches to health informatics applications are no longer ethical or acceptable when scientifically grounded evidence-based approaches are available and in use.
Aspect-based Financial Sentiment Analysis with Deep Neural Networks

Aspect-based financial sentiment analysis, which aims to classify the text instance into a pre-defined aspect class and predict the sentiment score for the mentioned target. In this paper, we propose a neural network model, Attention-based LSTM model with the Aspect information (ALA), to solve the financial opinion mining problem introduced by the WWW 2018 shared task. The proposed neural network model can adapt to the financial dataset so that the neural network can effectively understand the semantic information of the short text. We evaluate our model with the 10-fold cross-validation, and we compare our model with a variety of related deep neural network models.
Cognitive/Academic Language Proficiency, Linguistic Interdependence, the Optimum Age Question and Some Other Matters. Working Papers on Bilingualism, No. 19.

The-existence of a global language proficiençy factor is discussed. This factor, cognitive/academic language proficiency (Calk), As directly related to TO and to other aspects.of academic achievement. It accounts for the bulk of reliable variance in a wide variety of language learning measures, Three propositions concerning CALP arereviewed. (1) CALP can. be empirically distinguished from 'interpersonal communicative skills such as accent and fluency in first language (L1) and second language (L2) . (2) CALP proficiencies' in botti 0 and L2 are manifestations of the saserunderlying dimension. (3) Because 'the -same dimension underlies CALP in both L1• and L2, older learners, whose proficiency is better developed, will acquire 12 CALP more rapidly than younger learners. The relevance of . this analysis for the concepts of semilingualism, code-switching, and bilingual education is outlined. Semilingualism is a manifestation of low CALP in both languages. CALP will' be less active and effective when the L1 and the L2 are very dissimilar. In the presence of negative affective variables such as low motivation, CALP will not be applied. to learning L2. If motivational involvement and'adequate ~ "exposure to an L1 or L2 exist, CALP will' be promoted in both Languages regardless of which is the language of instruction. (PMJ)
Fungal Chitin Dampens Inflammation through IL-10 Induction Mediated by NOD2 and TLR9 Activation

Chitin is an essential structural polysaccharide of fungal pathogens and parasites, but its role in human immune responses remains largely unknown. It is the second most abundant polysaccharide in nature after cellulose and its derivatives today are widely used for medical and industrial purposes. We analysed the immunological properties of purified chitin particles derived from the opportunistic human fungal pathogen Candida albicans, which led to the selective secretion of the anti-inflammatory cytokine IL-10. We identified NOD2, TLR9 and the mannose receptor as essential fungal chitin-recognition receptors for the induction of this response. Chitin reduced LPS-induced inflammation in vivo and may therefore contribute to the resolution of the immune response once the pathogen has been defeated. Fungal chitin also induced eosinophilia in vivo, underpinning its ability to induce asthma. Polymorphisms in the identified chitin receptors, NOD2 and TLR9, predispose individuals to inflammatory conditions and dysregulated expression of chitinases and chitinase-like binding proteins, whose activity is essential to generate IL-10-inducing fungal chitin particles in vitro, have also been linked to inflammatory conditions and asthma. Chitin recognition is therefore critical for immune homeostasis and is likely to have a significant role in infectious and allergic disease. Authors Summary Chitin is the second most abundant polysaccharide in nature after cellulose and an essential component of the cell wall of all fungal pathogens. The discovery of human chitinases and chitinase-like binding proteins indicates that fungal chitin is recognised by cells of the human immune system, shaping the immune response towards the invading pathogen. We show that three immune cell receptors– the mannose receptor, NOD2 and TLR9 recognise chitin and act together to mediate an anti-inflammatory response via secretion of the cytokine IL-10. This mechanism may prevent inflammation-based damage during fungal infection and restore immune balance after an infection has been cleared. By increasing the chitin content in the cell wall pathogenic fungi may influence the immune system in their favour, by down-regulating protective inflammatory immune responses. Furthermore, gene mutations and dysregulated enzyme activity in the described chitin recognition pathway are implicated in inflammatory conditions such as Crohn's Disease and asthma, highlighting the importance of the discovered mechanism in human health.
Automatically Generating Wikipedia Info-boxes from Wikidata

Info-boxes provide a summary of the most important meta-data relating to a particular entity described by a Wikipedia article. However, many articles have no info-box or have info-boxes with only minimal information; furthermore, there is a huge disparity between the level of detail available for info-boxes in English articles and those for other languages. Wikidata has been proposed as a central repository of facts to try to address such disparities, and has been used as a source of information to generate info-boxes. However, current processes still rely on human intervention either to create generic templates for entities of a given type or to create a specific info-box for a specific article in a specific language. As such, there are still many articles of Wikipedia without info-boxes but where relevant data are provided by Wikidata. In this paper, we investigate fully automatic methods to generate info-boxes for Wikipedia from the Wikidata knowledge graph. The primary challenge is to create ranking mechanisms that provide an intuitive prioritisation of the facts associated with an entity. We discuss this challenge, propose several straightforward metrics to prioritise information in info-boxes, and present an initial user evaluation to compare the quality of info-boxes generated by various metrics.
Identification of BING-4 Cancer Antigen Translated From an Alternative Open Reading Frame of a Gene in the Extended MHC Class II Region Using Lymphocytes From a Patient With a Durable Complete Regression Following Immunotherapy

Multiple human cancer Ags have been identified, although little is known concerning which would be most effectively used in cancer immunotherapy. To gain insight into the selection of appropriate Ags, the immunologic reactivity of a patient who had a durable complete regression of melanoma metastases was measured. PBMCs were directly cloned using the monoclonal anti-CD3 Ab OKT3 and IL-2 without any bias introduced by previous culture. A lymphocyte clone recognized a previously unknown shared melanoma Ag that was identified as the BING-4 protein encoded in a gene-rich region of the extended class II MHC. The HLA-A2-restricted BING-4 immunodominant peptide was translated from a 10-aa-long alternative open reading frame. In vitro sensitization against this peptide generated lymphocytes reactive against HLA-A2+ melanomas. Real-time semiquantitative RT-PCR analysis revealed that 8 of 15 melanoma cell lines overexpressed BING-4, and this correlated with recognition by lymphocytes. Overexpression was not found in normal tissues or other tumor types. Thus, BING-4 represents another candidate Ag for possible use in the immunotherapy of patients with melanoma.
Inhibition of HIV‐1 entry by antibodies: potential viral and cellular targets

Vaccine‐induced antibodies that interfere with viral entry are the protective correlate of most existing prophylactic vaccines. However, for highly variable viruses such as HIV‐1, the ability to elicit broadly neutralizing antibody responses through vaccination has proven to be extremely difficult. The major targets for HIV‐1 neutralizing antibodies are the viral envelope glycoprotein trimers on the surface of the virus that mediate receptor binding and entry. HIV‐1 has evolved many mechanisms on the surface of envelope glycoproteins to evade antibody‐mediated neutralization, including the masking of conserved regions by glycan, quaternary protein interactions and the presence of immunodominant variable elements. The primary challenge in the development of an HIV‐1 vaccine that elicits broadly neutralizing antibodies therefore lies in the design of suitable envelope glycoprotein immunogens that circumvent these barriers. Here, we describe neutralizing determinants on the viral envelope glycoproteins that are defined by their function in receptor binding or by rare neutralizing antibodies isolated from HIV‐infected individuals. We also describe the nonvariable cellular receptors involved in the HIV‐1 entry process, or other cellular proteins, and ongoing studies to determine if antibodies against these proteins have efficacy as therapeutic reagents or, in some cases, as vaccine targets to interfere with HIV‐1 entry.
Could Simple Procedures Minimize Hysterectomy in Management of Placenta Accreta

Introduction: The incidence of placenta accreta (PA) is rising as a consequence of increased number of cesarean sections and advancing maternal age, both being independent risk factors. Severe postpartum hemorrhage (PPH) is a leading direct cause of maternal morbidity and mortality . Major surgical interventions like Hysterectomy, ligation of major pelvic vessels and massive blood transfusions are required to save the maternal life. Patients Methods: Fifteen cases of PA were included in the period from August 2014 to may 2015 in Obstetrics and Gynecology Department diagnosed by US and MRI. Preoperative evaluation and Laboratory investigations were done and Cross matched blood were done. Three step simple procedure was applied to all these 15 cases and we assessed its success in minimizing hysterectomy and ligation of major vessels. The procedure include first step: double ligation of uterine artery on both sides before and after placental removal, second step suturing the placental bed and third step is insertion of triple way catheter through the cervix and inflation to 50 cc saline to compress and drain bleeding. Results: The 3 step procedure was successful in minimizing major surgical interventions in all patients because neither patients required hysterectomy nor need Vascular interventions at all. There were no need for massive blood transfusions maximum of 3 -4 units of blood and the need of FFP was limited to 4 cases (26.6%) Complications were present in 6 cases (40%) and were: 2 cases (13.3%) of Bladder injury and 2 cases (13.3%) of pyrexia, 1 case (6.66%) of pyometria and 1 case (6.66%) of wound disruption. Conclusions: Three step procedure is a simple procedure and successful in minimizing major surgical interventions in PA management.
Newborn infants perceive abstract numbers

Although infants and animals respond to the approximate number of elements in visual, auditory, and tactile arrays, only human children and adults have been shown to possess abstract numerical representations that apply to entities of all kinds (e.g., 7 samurai, seas, or sins). Do abstract numerical concepts depend on language or culture, or do they form a part of humans' innate, core knowledge? Here we show that newborn infants spontaneously associate stationary, visual-spatial arrays of 4–18 objects with auditory sequences of events on the basis of number. Their performance provides evidence for abstract numerical representations at the start of postnatal experience.
In vivo detection of single cells by MRI

The use of high‐relaxivity, intracellular contrast agents has enabled MRI monitoring of cell migration through and homing to various tissues, such as brain, spinal cord, heart, and muscle. Here it is shown that MRI can detect single cells in vivo, homing to tissue, following cell labeling and transplantation. Primary mouse hepatocytes were double‐labeled with green fluorescent 1.63‐μm iron oxide particles and red fluorescent endosomal labeling dye, and injected into the spleens of recipient mice. This is a common hepatocyte transplantation paradigm in rodents whereby hepatocytes migrate from the spleen to the liver as single cells. One month later the animals underwent in vivo MRI and punctuated, dark contrast regions were detected scattered through the livers. MRI of perfused, fixed samples and labeled hepatocyte phantoms in combination with histological evaluation confirmed the presence of dispersed single hepatocytes grafted into the livers. Appropriate controls were used to determine whether the observed contrast could have been due to dead cells or free particles, and the results confirmed that the contrast was due to disperse, single cells. Detecting single cells in vivo opens the door to a number of experiments, such as monitoring rare cellular events, assessing the kinetics of stem cell homing, and achieving early detection of metastases. Magn Reson Med, 2006. Published 2006 Wiley‐Liss, Inc.
A vaccine for malaria.

It's been a long time coming, and indeed we are still not there yet, but it is becoming increasingly clear that we really do have the first effective vaccine against a parasitic disease in humans. If there are no unforeseen disasters, the RTS,S/AS01 Plasmodium falciparum malaria vaccine should become available in just over 3 years. The World Health Organization (WHO) has already taken the unusual step of indicating that it could recommend this first malaria vaccine for use in some African countries as early as 2015, depending on the full phase 3 trial results that will become available in 2014.
Child and Mother Play in Three U.s. Cultural Groups: Comparisons and Associations the Importance of Studying Immigrant Children's Play

Child and mother play (n ϭ 113 20-month-olds) among South American Latino immigrants, Japanese immigrants, and European Americans in the United States was investigated. Culturally universal patterns of play dominated the findings. For example, no cultural differences in the prevalence of exploratory or symbolic play were found for either children or their mothers. Regardless of their culture, boys engaged in significantly more exploratory and less symbolic play than did girls when they played by themselves. Few relations were found between child play in the two play sessions. Across cultural groups, children's exploratory play was significantly positively related to both maternal demonstrations and solicitations of exploratory play. The results identify which realms of child growth, parenting, and family function call for special attention and cultural sensitivity, as well as which do not, in the dynamics of immigrant families. Observation of mothers and children engaged in universal , developmentally appropriate activities can help to reveal cultural influences on children's development (Rogoff, 2003). Play constitutes such an activity during the 2nd year of life. Cross-cultural research on children's play has highlighted the importance of culture-specific practices in struc-turing and organizing the environment in which children's social interactions and play activities take place (see Born-During the 2nd year of life, children's play normatively moves from being exploratory and object oriented to being symbolic and pretense oriented. During the sensorimotor period, children's initial interactions with objects are exploratory in nature, and their schemas characterize objects (e.g., a ball) as something simply to be physically manipulated (Piaget, 1951/1962). However, as children begin to engage in symbolic play, they use familiar objects in new ways, for example, by pretending that a ball is an orange that they are eating. Although there are individual differences in play development and related cognitive abilities, across cultures achieving representational competence is one of the principal developmental tasks of the 2nd year of However, cultural variation in play is also evident (Bornstein, 2007). Immigrant families may find culture-specific aspects of play in their culture of destination particularly challenging or perplexing during the process of acculturation, and culture-specific aspects of play from the immigrants' culture of origin may be interpreted by clini-cians, teachers, or others as problematic simply because they differ from those of the culture of destination. The study of immigrant children's play is important for a variety of reasons. First, immigration is a central social and psychological concern today. For example, …
Potent induction of B- and T-cell immunity against human carcinoembryonic antigen-expressing tumors in human carcinoembryonic antigen transgenic mice mediated by direct lentivector injection

The applicability of immunotherapy would be dramatically broadened to a greater number of recipients if direct “off-the-shelf” products could be engineered to engender functionally potent immune responses against true “self”-tumor antigens. This would obviate the need for ex vivo culture of dendritic cells or T cells on a patient-by-patient basis, for example. The carcinoembryonic antigen (CEA) is a glycoprotein expressed in normal gut epithelium that is up-regulated in the majority of colon cancers, non-small cell lung cancers, and half of all breast cancers. Such properties make CEA an excellent and important target for cancer immunotherapy. In this study, we show stabilization of 14-day established s.c. mGC4CEA tumors in human CEA (huCEA) transgenic mice following two direct low-dose injections of 0.15 × 106 transducing units of a lentiviral vector (LV) that directs expression of huCEA (LV-huCEA). This stabilization result was reproducible and detailed analyses including antibody assays, multiplex cytokine analyses on unstimulated splenocytes, lymph node cell characterizations, tetramer staining, and immunofluorescence staining of tumor sections showed that this outcome correlated with both a cellular and humoral immune response. Similar tumor outcomes were not seen when mice were vaccinated with a control LV that engineered expression of enGFP only. The long-term potency of this vaccination strategy was also studied and revealed the requirement for maintenance of tumor antigen-specific immunity for efficient tumor control. These data support the use of direct injections of low doses of LV-huCEA for enhancement of tumor immunotherapy directed against CEA. [Mol Cancer Ther 2009;8(3):OF692–11]
Processive DNA Demethylation via DNA Deaminase-Induced Lesion Resolution

Base modifications of cytosine are an important aspect of chromatin biology, as they can directly regulate gene expression, while DNA repair ensures that those modifications retain genome integrity. Here we characterize how cytosine DNA deaminase AID can initiate DNA demethylation. In vitro, AID initiated targeted DNA demethylation of methyl CpGs when in combination with DNA repair competent extracts. Mechanistically, this is achieved by inducing base alterations at or near methyl-cytosine, with the lesion being resolved either via single base substitution or a more efficient processive polymerase dependent repair. The biochemical findings are recapitulated in an in vivo transgenic targeting assay, and provide the genetic support of the molecular insight into DNA demethylation. This targeting approach supports the hypothesis that mCpG DNA demethylation can proceed via various pathways and mCpGs do not have to be targeted to be demethylated.