Blimp-1-dependent and -independent natural antibody production by B-1 and B-1-derived plasma cells.

Natural antibodies contribute to tissue homeostasis and protect against infections. They are secreted constitutively without external antigenic stimulation. The differentiation state and regulatory pathways that enable continuous natural antibody production by B-1 cells, the main cellular source in mice, remain incompletely understood. Here we demonstrate that natural IgM-secreting B-1 cells in the spleen and bone marrow are heterogeneous, consisting of (a) terminally differentiated B-1-derived plasma cells expressing the transcriptional regulator of differentiation, Blimp-1, (b) Blimp-1+, and (c) Blimp-1neg phenotypic B-1 cells. Blimp-1neg IgM-secreting B-1 cells are not simply intermediates of cellular differentiation. Instead, they secrete similar amounts of IgM in wild-type and Blimp-1-deficient (PRDM-1ΔEx1A) mice. Blimp-1neg B-1 cells are also a major source of IgG3. Consequently, deletion of Blimp-1 changes neither serum IgG3 levels nor the amount of IgG3 secreted per cell. Thus, the pool of natural antibody-secreting B-1 cells is heterogeneous and contains a distinct subset of cells that do not use Blimp-1 for initiation or maximal antibody secretion

Giant magnons and non-maximal giant gravitons

We produce the open strings on $\mathbb{R}\times S^{2}$ that correspond to the solutions of integrable boundary sine-Gordon theory by making use of the $N$-magnon solutions provided in \cite{KPV} together with explicit moduli. Relating the two boundary parameters in a special way we describe the scattering of giant magnons with non-maximal $Y=0$ giant gravitons and calculate the leading contribution to the associated magnon scattering phase.Comment: 34 pages, 8 figure

Challenges and opportunities for implementing integrated mental health care: a district level situation analysis from five low- and middle-income countries.

BACKGROUND: Little is known about how to tailor implementation of mental health services in low- and middle-income countries (LMICs) to the diverse settings encountered within and between countries. In this paper we compare the baseline context, challenges and opportunities in districts in five LMICs (Ethiopia, India, Nepal, South Africa and Uganda) participating in the PRogramme for Improving Mental health carE (PRIME). The purpose was to inform development and implementation of a comprehensive district plan to integrate mental health into primary care. METHODS: A situation analysis tool was developed for the study, drawing on existing tools and expert consensus. Cross-sectional information obtained was largely in the public domain in all five districts. RESULTS: The PRIME study districts face substantial contextual and health system challenges many of which are common across sites. Reliable information on existing treatment coverage for mental disorders was unavailable. Particularly in the low-income countries, many health service organisational requirements for mental health care were absent, including specialist mental health professionals to support the service and reliable supplies of medication. Across all sites, community mental health literacy was low and there were no models of multi-sectoral working or collaborations with traditional or religious healers. Nonetheless health system opportunities were apparent. In each district there was potential to apply existing models of care for tuberculosis and HIV or non-communicable disorders, which have established mechanisms for detection of drop-out from care, outreach and adherence support. The extensive networks of community-based health workers and volunteers in most districts provide further opportunities to expand mental health care. CONCLUSIONS: The low level of baseline health system preparedness across sites underlines that interventions at the levels of health care organisation, health facility and community will all be essential for sustainable delivery of quality mental health care integrated into primary care

Incremental dimension reduction of tensors with random index

We present an incremental, scalable and efficient dimension reduction technique for tensors that is based on sparse random linear coding. Data is stored in a compactified representation with fixed size, which makes memory requirements low and predictable. Component encoding and decoding are performed on-line without computationally expensive re-analysis of the data set. The range of tensor indices can be extended dynamically without modifying the component representation. This idea originates from a mathematical model of semantic memory and a method known as random indexing in natural language processing. We generalize the random-indexing algorithm to tensors and present signal-to-noise-ratio simulations for representations of vectors and matrices. We present also a mathematical analysis of the approximate orthogonality of high-dimensional ternary vectors, which is a property that underpins this and other similar random-coding approaches to dimension reduction. To further demonstrate the properties of random indexing we present results of a synonym identification task. The method presented here has some similarities with random projection and Tucker decomposition, but it performs well at high dimensionality only (n>10^3). Random indexing is useful for a range of complex practical problems, e.g., in natural language processing, data mining, pattern recognition, event detection, graph searching and search engines. Prototype software is provided. It supports encoding and decoding of tensors of order >= 1 in a unified framework, i.e., vectors, matrices and higher order tensors.Comment: 36 pages, 9 figure

Conceptualising a Dynamic Technology Practice in Education Using Argyris and Schön's Theory of Action

Despite substantial national effort to integrate technology in education, it seems that practitioners in the education system are not working in line with the given policy. Evidence from large-scale studies of students’ technology practices at school over the last decade show disparities in student practices. The observed gap between the micro and the macro level call for a closer exploration. Research that explores the influence of social and organizational factors may be useful for understanding the processes behind such gaps. Argyris and Schön’s ‘Theory of Action’ (1978) is proposed as an example of an organizational theory that can be adopted in educational technology research to move towards understanding the complexities of technology practice. To encourage discourse and application of Argyris and Schön’s theory in the field of educational technology research, this paper introduces the theory, a review of its empirical application in research of teacher educations’ technology practice and relevant conceptual work. The paper presents a conceptual framework based on Argyris and Schön’s theory that has been developed through two recent studies, and invites its application in future research and development

Oral ulcer as an exclusive sign of gastric cancer: report of a rare case

BACKGROUND: The oral cavity is a rare but occasional target for metastases, which may masquerade as various benign and inflammatory lesions, and sometimes also be asymptomatic. Oral metastatic lesions have been described in various cancers, particularly lung, breast and kidney carcinoma. CASE PRESENTATION: We here describe an uncommon case of a hard palate mucosa and gingival metastasis from gastric carcinoma that was originally diagnosed as a periodontal disease. Histopathological examination of a biopsy of the lesion revealed a signet-ring cell carcinoma, and a subsequent biopsy of an ulcerated stomach lesion showed a poorly differentiated gastric carcinoma. The patient underwent gastric resection but died of heart failure on the tenth postoperative day; a post-mortem examination revealed a residual bilateral ovarian infiltration by gastric carcinoma (Krukenberg's tumor). CONCLUSION: An occult carcinoma of the stomach may rarely metastasise to the oral cavity even as a first and exclusive manifestation; it is important to bear this possibility in mind because such conditions may mimic a benign disease

Clinical trial of laronidase in Hurler syndrome after hematopoietic cell transplantation.

BackgroundMucopolysaccharidosis I (MPS IH) is a lysosomal storage disease treated with hematopoietic cell transplantation (HCT) because it stabilizes cognitive deterioration, but is insufficient to alleviate all somatic manifestations. Intravenous laronidase improves somatic burden in attenuated MPS I. It is unknown whether laronidase can improve somatic disease following HCT in MPS IH. The objective of this study was to evaluate the effects of laronidase on somatic outcomes of patients with MPS IH previously treated with HCT.MethodsThis 2-year open-label pilot study of laronidase included ten patients (age 5-13 years) who were at least 2 years post-HCT and donor engrafted. Outcomes were assessed semi-annually and compared to historic controls.ResultsThe two youngest participants had a statistically significant improvement in growth compared to controls. Development of persistent high-titer anti-drug antibodies (ADA) was associated with poorer 6-min walk test (6MWT) performance; when patients with high ADA titers were excluded, there was a significant improvement in the 6MWT in the remaining seven patients.ConclusionsLaronidase seemed to improve growth in participants <8 years old, and 6MWT performance in participants without ADA. Given the small number of patients treated in this pilot study, additional study is needed before definitive conclusions can be made

A Comparative Study of Human TLR 7/8 Stimulatory Trimer Compositions in Influenza A Viral Genomes

Background: Variation in the genomes of single-stranded RNA viruses affects their infectivity and pathogenicity in two ways. First, viral genome sequence variations lead to changes in viral protein sequences and activities. Second, viral genome sequence variation produces diversity at the level of nucleotide composition and diversity in the interactions between viral RNAs and host toll-like receptors (TLRs). A viral genome-typing method based on this type of diversity has not yet been established. Methodology/Principal Findings: In this study, we propose a novel genomic trait called the ‘‘TLR stimulatory trimer composition’ ’ (TSTC) and two quantitative indicators, Score S and Score N, named ‘‘TLR stimulatory scores’ ’ (TSS). Using the complete genome sequences of 10,994 influenza A viruses (IAV) and 251 influenza B viruses, we show that TSTC analysis reveals the diversity of Score S and Score N among the IAVs isolated from various hosts. In addition, we show that low values of Score S are correlated with high pathogenicity and pandemic potential in IAVs. Finally, we use Score S and Score N to construct a logistic regression model to recognize IAV strains that are highly pathogenic or have high pandemic potential. Conclusions/Significance: Results from the TSTC analysis indicate that there are large differences between human and avian IAV genomes (except for segment 3), as illustrated by Score S. Moreover, segments 1, 2, 3 and 4 may be majo