Betaine chemistry, roles, and potential use in liver disease

Background Betaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is utilized in the kidney primarily as an osmoprotectant, whereas in the liver its primary role is in metabolism as a methyl group donor. In both organs, a specific betaine transporter mediates cellular uptake of betaine from plasma. The abundance of both betaine and the betaine transporter in liver greatly exceeds that of other organs. Scope of review The remarkable contributions of betaine to normal human and animal health are summarized together with a discussion of the mechanisms and potential beneficial effects of dietary betaine supplements on liver disease. Major conclusions A significant amount of data from animal models of liver disease indicates that administration of betaine can halt and even reverse progression of the disruption of liver function. Betaine is well-tolerated, inexpensive, effective over a wide range of doses, and is already used in livestock feeding practices. General significance The accumulated data indicate that carefully controlled additional investigations in humans are merited. The focus should be on the long-term use of betaine in large patient populations with liver diseases characterized by development of fatty liver, especially non-alcoholic fatty liver disease and alcoholic liver disease

Incremental Composition in Distributional Semantics

Despite the incremental nature of Dynamic Syntax (DS), the semantic grounding of it remains that of predicate logic, itself grounded in set theory, so is poorly suited to expressing the rampantly context-relative nature of word meaning, and related phenomena such as incremental judgements of similarity needed for the modelling of disambiguation. Here, we show how DS can be assigned a compositional distributional semantics which enables such judgements and makes it possible to incrementally disambiguate language constructs using vector space semantics. Building on a proposal in our previous work, we implement and evaluate our model on real data, showing that it outperforms a commonly used additive baseline. In conclusion, we argue that these results set the ground for an account of the non-determinism of lexical content, in which the nature of word meaning is its dependence on surrounding context for its construal

Incremental Composition in Distributional Semantics

Despite the incremental nature of Dynamic Syntax (DS), the semantic grounding of it remains that of predicate logic, itself grounded in set theory, so is poorly suited to expressing the rampantly context-relative nature of word meaning, and related phenomena such as incremental judgements of similarity needed for the modelling of disambiguation. Here, we show how DS can be assigned a compositional distributional semantics which enables such judgements and makes it possible to incrementally disambiguate language constructs using vector space semantics. Building on a proposal in our previous work, we implement and evaluate our model on real data, showing that it outperforms a commonly used additive baseline. In conclusion, we argue that these results set the ground for an account of the non-determinism of lexical content, in which the nature of word meaning is its dependence on surrounding context for its construal

Distributed utterances

I propose an apparatus for handling intrasentential change in context. The standard approach has problems with sentences with multiple occurrences of the same demonstrative or indexical. My proposal involves the idea that contexts can be complex. Complex contexts are built out of (“simple”) Kaplanian contexts by ordered n-tupling. With these we can revise the clauses of Kaplan’s Logic of Demonstratives so that each part of a sentence is taken in a different component of a complex context. I consider other applications of the framework: to agentially distributed utterances (ones made partly by one speaker and partly by another); to an account of scare-quoting; and to an account of a binding-like phenomenon that avoids what Kit Fine calls “the antinomy of the variable.

Design and performance testing of quantitative real time PCR assays for influenza A and B viral load measurement

Background: The antiviral effect of anti-influenza drugs such as zanamivir may be demonstrated in patients as an increased rate of decline in viral load over a time course of treatment as compared with placebo. Historically this was measured using plaque assays, or Culture Enhanced Enzyme Linked Immunosorbent Assay (CE-ELISA). Objectives: to develop and characterise real time quantitative PCR (qPCR) assays to measure influenza A and B viral load in clinical samples, that offer improvements over existing methods, in particular virus infectivity assays. Study design: The dynamic range and robustness were established for the real time qPCR assays along with stability of the assay components. Cross validation of the real time PCR assays with CE-ELISA was performed by parallel testing of both serial dilutions of three different subtypes of cultured virus and a panel of influenza positive throat swab specimens. Results: the assays were specific for influenza A and B and the dynamic ranges were at least seven logs. The assay variability was within acceptable limits but increased towards the lower limit of quantification, which was 3.33 log10 viral cDNA copies/ml of virus transport medium (ten viral RNA copies/PCR). The components of the assay were robust enough to withstand extended storage and several freeze–thawcycles. For the real time PCR assays the limit of quantification was equivalent to the virus infectivity cut off, which equates to a 93-fold increase in sensitivity. Conclusion: Well characterised real time PCR assays offer significant improvements over the existing methods for measuring the viral load of strains of influenza A and B in clinical specimens

Completability vs (In)completeness

In everyday conversation, no notion of “complete sentence” is required for syntactic licensing. However, so-called “fragmentary”, “incomplete”, and abandoned utterances are problematic for standard formalisms. When contextualised, such data show that (a) non-sentential utterances are adequate to underpin agent coordination, while (b) all linguistic dependencies can be systematically distributed across participants and turns. Standard models have problems accounting for such data because their notions of ‘constituency’ and ‘syntactic domain’ are independent of performance considerations. Concomitantly, we argue that no notion of “full proposition” or encoded speech act is necessary for successful interaction: strings, contents, and joint actions emerge in conversation without any single participant having envisaged in advance the outcome of their own or their interlocutors’ actions. Nonetheless, morphosyntactic and semantic licensing mechanisms need to apply incrementally and subsententially. We argue that, while a representational level of abstract syntax, divorced from conceptual structure and physical action, impedes natural accounts of subsentential coordination phenomena, a view of grammar as a “skill” employing domain-general mechanisms, rather than fixed form-meaning mappings, is needed instead. We provide a sketch of a predictive and incremental architecture (Dynamic Syntax) within which underspecification and time-relative update of meanings and utterances constitute the sole concept of “syntax”

Self-Efficacy and Mental Health Services Provided by Rural and Frontier Oncology Social Workers

This pilot study explores the relationship between self-efficacy and professional behaviors of a non-random membership sample of the Association of Oncology Social Work (AOSW) who practice in rural and frontier settings (N = 19). The New Generalized Self-Efficacy (NGSE) scale was used to measure provider self-efficacy; a researcher-designed questionnaire was used to assess the professional behaviors of conducting mental health assessments and providing supportive counseling to individuals diagnosed with cancer. Pearson correlation and two-sample t-tests were used to analyze data. While study results did not elucidate relationships explored, results revealed a disparity between participants’ overall high sense of professional preparedness and comfort conducting mental health assessments and the regularity with which they perform these functions of oncology patient care

Role of N-glycosylation in renal betaine transport

The osmolyte and folding chaperone betaine is transported by the renal Na+-coupled GABA (γ-aminobutyric acid) symporter BGT-1 (betaine/GABA transporter 1), a member of the SLC6 (solute carrier 6) family. Under hypertonic conditions, the transcription, translation and plasma membrane (PM) insertion of BGT-1 in kidney cells are significantly increased, resulting in elevated betaine and GABA transport. Re-establishing isotonicity involves PM depletion of BGT-1. The molecular mechanism of the regulated PM insertion of BGT-1 during changes in osmotic stress is unknown. In the present study, we reveal a link between regulated PM insertion and N-glycosylation. Based on homology modelling, we identified two sites (Asn171 and Asn183) in the extracellular loop 2 (EL2) of BGT-1, which were investigated with respect to trafficking, insertion and transport by immunogold-labelling, electron microscopy (EM), mutagenesis and two-electrode voltage clamp measurements in Xenopus laevis oocytes and uptake of radiolabelled substrate into MDCK (Madin–Darby canine kidney) and HEK293 (human embryonic kidney) cells. Trafficking and PM insertion of BGT-1 was clearly promoted by N-glycosylation in both oocytes and MDCK cells. Moreover, association with N-glycans at Asn171 and Asn183 contributed equally to protein activity and substrate affinity. Substitution of Asn171 and Asn183 by aspartate individually caused no loss of BGT-1 activity, whereas the double mutant was inactive, suggesting that N-glycosylation of at least one of the sites is required for function. Substitution by alanine or valine at either site caused a dramatic loss in transport activity. Furthermore, in MDCK cells PM insertion of N183D was no longer regulated by osmotic stress, highlighting the impact of N-glycosylation in regulation of this SLC6 transporter

Articular contact in a three-dimensional model of the knee

This study is aimed at the analysis of articular contact in a three-dimensional mathematical model of the human knee-joint. In particular the effect of articular contact on the passive motion characteristics is assessed in relation to experimentally obtained joint kinematics. Two basically different mathematical contact descriptions were compared for this purpose. One description was for rigid contact and one for deformable contact. The description of deformable contact is based on a simplified theory for contact of a thin elastic layer on a rigid foundation. The articular cartilage was described either as a linear elastic material or as a non-linear elastic material. The contact descriptions were introduced in a mathematical model of the knee. The locations of the ligament insertions and the geometry of the articular surfaces were obtained from a joint specimen of which experimentally determined kinematic data were available, and were used as input for the model. The ligaments were described by non-linear elastic line elements. The mechanical properties of the ligaments and the articular cartilage were derived from literature data. Parametric model evaluations showed that, relative to rigid articular contact, the incorporation of deformable contact did not alter the motion characteristics in a qualitative sense, and that the quantitative changes were small. Variation of the elasticity of the elastic layer revealed that decreasing the surface stiffness caused the ligaments to relax and, as a consequence, increased the joint laxity, particularly for axial rotation. The difference between the linear and the non-linear deformable contact in the knee model was very small for moderate loading conditions. The motion characteristics simulated with the knee model compared very well with the experiments. It is concluded that for simulation of the passive motion characteristics of the knee, the simplified description for contact of a thin linear elastic layer on a rigid foundation is a valid approach when aiming at the study of the motion characteristics for moderate loading conditions. With deformable contact in the knee model, geometric conformity between the surfaces can be modelled as opposed to rigid contact which assumed only point contact

Impact testing to determine the mechanical properties of articular cartilage in isolation and on bone

The original publication is available at www.springerlink.comNon peer reviewedPostprin