The Courtroom Status of the Polygraph

This comment will inform the reader of the status and various uses of the polygraph available to the criminal attorney, with an emphasis on Ohio law

Interception of the Bycroft-Gowland Intermediate in the Enzymatic Macrocyclization of Thiopeptides

Thiopeptides are a broad class of macrocyclic, heavily modified peptide natural products that are unified by the presence of a substituted, nitrogen-containing heterocycle core. Early work indicated that this core might be fashioned from two dehydroalanines by an enzyme-catalyzed aza-[4 + 2] cycloaddition to give a cyclic-hemiaminal intermediate. This common intermediate could then follow a reductive path toward a dehydropiperidine, as in the thiopeptide thiostrepton, or an aromatization path to yield the pyridine groups observed in many other thiopeptides. Although several of the enzymes proposed to perform this cycloaddition have been reconstituted, only pyridine products have been isolated and any hemiaminal intermediates have yet to be observed. Here, we identify the conditions and substrates that decouple the cycloaddition from subsequent steps and allow interception and characterization of this long hypothesized intermediate. Transition state modeling indicates that the key amide-iminol tautomerization is the major hurdle in an otherwise energetically favorable cycloaddition. An anionic model suggests that deprotonation and polarization of this amide bond by TbtD removes this barrier and provides a sufficient driving force for facile (stepwise) cycloaddition. This work provides evidence for a mechanistic link between disparate cyclases in thiopeptide biosynthesis

Development and evaluation of an instrument for the critical appraisal of randomized controlled trials of natural products

<p>Abstract</p> <p>Background</p> <p>The efficacy of natural products (NPs) is being evaluated using randomized controlled trials (RCTs) with increasing frequency, yet a search of the literature did not identify a widely accepted critical appraisal instrument developed specifically for use with NPs. The purpose of this project was to develop and evaluate a critical appraisal instrument that is sufficiently rigorous to be used in evaluating RCTs of conventional medicines, and also has a section specific for use with single entity NPs, including herbs and natural sourced chemicals.</p> <p>Methods</p> <p>Three phases of the project included: 1) using experts and a Delphi process to reach consensus on a list of items essential in describing the identity of an NP; 2) compiling a list of non-NP items important for evaluating the quality of an RCT using systematic review methodology to identify published instruments and then compiling item categories that were part of a validated instrument and/or had empirical evidence to support their inclusion and 3) conducting a field test to compare the new instrument to a published instrument for usefulness in evaluating the quality of 3 RCTs of a NP and in applying results to practice.</p> <p>Results</p> <p>Two Delphi rounds resulted in a list of 15 items essential in describing NPs. Seventeen item categories fitting inclusion criteria were identified from published instruments for conventional medicines. The new assessment instrument was assembled based on content of the two lists and the addition of a Reviewer's Conclusion section. The field test of the new instrument showed good criterion validity. Participants found it useful in translating evidence from RCTs to practice.</p> <p>Conclusion</p> <p>A new instrument for the critical appraisal of RCTs of NPs was developed and tested. The instrument is distinct from other available assessment instruments for RCTs of NPs in its systematic development and validation. The instrument is ready to be used by pharmacy students, health care practitioners and academics and will continue to be refined as required.</p

Identification of chemosensory receptor genes in Manduca sexta and knockdown by RNA interference

Insects detect environmental chemicals via a large and rapidly evolving family of chemosensory receptor proteins. Although our understanding of the molecular genetic basis for Drosophila chemoreception has increased enormously in the last decade, similar understanding in other insects remains limited. The tobacco hornworm, Manduca sexta, has long been an important model for insect chemosensation, particularly from ecological, behavioral, and physiological standpoints. It is also a major agricultural pest on solanaceous crops. However, little sequence information and lack of genetic tools has prevented molecular genetic analysis in this species. The ability to connect molecular genetic mechanisms, including potential lineage-specific changes in chemosensory genes, to ecologically relevant behaviors and specializations in M. sexta would be greatly beneficial. Here, we sequenced transcriptomes from adult and larval chemosensory tissues and identified chemosensory genes based on sequence homology. We also used dsRNA feeding as a method to induce RNA interference in larval chemosensory tissues. We report identification of new chemosensory receptor genes including 17 novel odorant receptors and one novel gustatory receptor. Further, we demonstrate that systemic RNA interference can be used in larval olfactory neurons to reduce expression of chemosensory receptor transcripts. Together, our results further the development of M. sexta as a model for functional analysis of insect chemosensation

A systematic review of randomised controlled trials assessing effectiveness of prosthetic and orthotic interventions.

BACKGROUND: Assistive products are items which allow older people and people with disabilities to be able to live a healthy, productive and dignified life. It has been estimated that approximately 1.5% of the world's population need a prosthesis or orthosis. OBJECTIVE: The objective of this study was to systematically identify and review the evidence from randomized controlled trials assessing effectiveness and cost-effectiveness of prosthetic and orthotic interventions. METHODS: Literature searches, completed in September 2015, were carried out in fourteen databases between years 1995 and 2015. The search results were independently screened by two reviewers. For the purpose of this manuscript, only randomized controlled trials which examined interventions using orthotic or prosthetic devices were selected for data extraction and synthesis. RESULTS: A total of 342 randomised controlled trials were identified (319 English language and 23 non-English language). Only 4 of these randomised controlled trials examined prosthetic interventions and the rest examined orthotic interventions. These orthotic interventions were categorised based on the medical conditions/injuries of the participants. From these studies, this review focused on the medical condition/injuries with the highest number of randomised controlled trials (osteoarthritis, fracture, stroke, carpal tunnel syndrome, plantar fasciitis, anterior cruciate ligament, diabetic foot, rheumatoid and juvenile idiopathic arthritis, ankle sprain, cerebral palsy, lateral epicondylitis and low back pain). The included articles were assessed for risk of bias using the Cochrane Risk of Bias tool. Details of the clinical population examined, the type of orthotic/prosthetic intervention, the comparator/s and the outcome measures were extracted. Effect sizes and odds ratios were calculated for all outcome measures, where possible. CONCLUSIONS: At present, for prosthetic and orthotic interventions, the scientific literature does not provide sufficient high quality research to allow strong conclusions on their effectiveness and cost-effectiveness

A longitudinal study of vocabulary in L2 academic English writing of Arabic first-language students: development and measurement

This corpus based study investigates the lexical development of forty-two 'English as a Second language' (ESL) university students, using 340 formal examination essays, written at regular intervals over a period of twenty-seven months. One of the main research questions is how vocabulary growth during this twenty-seven month period can be modelled. It was assumed, after Laufer (1994), thjilt the growth of basic words would . follow a curvilinear pattern and flatten out towards the end of the period, whereas the learning curve for advanced words would follow a linear pattern with constant growth, continuing perhaps even at higher proficiency levels. A further question was whether, and to what extent, trained and experienced English as a Foreign Language (EFL) teachers (and International English Language Testing System (IElTS) raters) would base their ratings of the essays on vocabulary richness. Earlier research (Malvern & Richards 2002) indicates that teacher judgements in oral interviews might not be influenced by the lexical diversity of the candidate's performance. The question is whether this might also apply.to written texts. The handwritten essays were all transcribed, verbatim, and prepared for processing within predetermined parameters. Measures of development included the use of advanced words (AWL), Malvern and Richards' lexical diversity D (LDV) (requiring the texts to be put into the CHAT format), P_Lex (PL), Guiraud (G), Guiraud Advanced (GA) and Limiting Relative Diversity (LRD). Several regression analyses show that almost all measures display a similar pattern of development and log-linear fitted lines did increase the explained variance slightly. Against the general pattern of vocabulary development, the study also examines individual differences and finds that these do not conform to the same pattern as the group, which leads to a high amount of unexplained variance in the regression analyses. Lexical development as shown by the measures was compared to raters' assessments of vocabulary. Holistic ratings were also given in an attempt to gauge deployment and use of the vocabulary, and some significant correlations were found between the ratings and some measures. This suggests that raters are influenced by other factors such as organisation and grammar and that rating is not based on lexical richness, which agrees with the findings on oral interviews, found in the literature. A high correlation between the lexical and holistic ratings suggests perhaps that raters do not judge vocabulary richness separately but give only holistic judgments.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

The use and development of academic vocabulary in L2 writing: a longitudinal investigation

Recent years have seen the increasing use of vocabulary frequency lists such as \u27the 1,000 most frequent words in English\u27 to assess the difficulty of reading texts, as well as the development of learners\u27 language. This paper reports on a longitudinal study of university essays in English, written every ten weeks under examination conditions, over a period of two years by 42 Arabic-speaking students. The expectation was that students\u27 use of academic vocabulary would begin with those words used most frequently in academic English and, as their vocabulary developed, draw increasingly from less commonly-used words. The evidence from this study of written output suggests that the frequency lists, which are based on academic usage by (near-)native users of English, may not be as applicable as thought for modelling the development of vocabulary use in learners of English as a second or foreign language