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Find video protocols related to scientific articles indexed in Pubmed.
Perceptual and acoustic analysis of lexical stress in Greek speakers with dysarthria.
Clin Linguist Phon
PUBLISHED: 07-08-2014
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The study reported in this paper investigated the abilities of Greek speakers with dysarthria to signal lexical stress at the single word level. Three speakers with dysarthria and two unimpaired control participants were recorded completing a repetition task of a list of words consisting of minimal pairs of Greek disyllabic words contrasted by lexical stress location only. Fourteen listeners were asked to determine the attempted stress location for each word pair. Acoustic analyses of duration and intensity ratios, both within and across words, were undertaken to identify possible acoustic correlates of the listeners' judgments concerning stress location. Acoustic and perceptual data indicate that while each participant with dysarthria in this study had some difficulty in signaling stress unambiguously, the pattern of difficulty was different for each speaker. Further, it was found that the relationship between the listeners' judgments of stress location and the acoustic data was not conclusive.
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Considerations and evidence for an ADHD outcome measure.
Acad Pediatr
PUBLISHED: 06-10-2014
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The 2011 American Academy of Pediatrics attention-deficit/hyperactivity disorder (ADHD) guideline emphasizes monitoring and measuring outcomes of children diagnosed with ADHD; however, recommendations for how to measure improvement are less clear. A long-term goal was to develop an outcome measure that assesses the quality of care for children with ADHD. As a first step in that process, we conducted a literature synthesis on the efficacy and effectiveness of guideline-recommended ADHD treatments on patient outcomes.
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Patient reported outcomes as indicators of pediatric health care quality.
Acad Pediatr
PUBLISHED: 06-02-2014
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Health care reform has increased demand for pediatric health care quality evaluations, particularly those that assess the impact of care on patient and population health outcomes. Many of today's most common childhood conditions are characterized by symptoms, behaviors, and functional limitations that are best assessed as patient reported outcomes (PROs). Although they remain greatly underutilized, PROs have the potential to improve pediatric health care quality assessment at the point of care and through system-level performance evaluations. The functions, benefits, and challenges of these PRO applications are described and illustrated in case examples. Although challenges remain, numerous methodological and technical innovations facilitate the use of PROs as health care quality metrics. These include advances in PRO measure development methodologies, the integration of PRO measures into electronic health records, and developing consensus among providers that PROs provide valuable information that can be used to enhance patient care. Although additional work is needed to address remaining methodological challenges, pediatric PROs are increasingly recognized as valuable indicators of health care quality in the clinical environment and as measures of organization- and provider-level performance.
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XIAP restricts TNF- and RIP3-dependent cell death and inflammasome activation.
Cell Rep
PUBLISHED: 04-10-2014
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X-linked inhibitor of apoptosis protein (XIAP) has been identified as a potent regulator of innate immune responses, and loss-of-function mutations in XIAP cause the development of the X-linked lymphoproliferative syndrome type 2 (XLP-2) in humans. Using gene-targeted mice, we show that loss of XIAP or deletion of its RING domain lead to excessive cell death and IL-1? secretion from dendritic cells triggered by diverse Toll-like receptor stimuli. Aberrant IL-1? secretion is TNF dependent and requires RIP3 but is independent of cIAP1/cIAP2. The observed cell death also requires TNF and RIP3 but proceeds independently of caspase-1/caspase-11 or caspase-8 function. Loss of XIAP results in aberrantly elevated ubiquitylation of RIP1 outside of TNFR complex I. Virally infected Xiap(-/-) mice present with symptoms reminiscent of XLP-2. Our data show that XIAP controls RIP3-dependent cell death and IL-1? secretion in response to TNF, which might contribute to hyperinflammation in patients with XLP-2.
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Cloning of recombinant monoclonal antibodies from hybridomas in a single mammalian expression plasmid.
Methods Mol. Biol.
PUBLISHED: 02-12-2014
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Antibodies are an integral part of biological and medical research. In addition, immunoglobulins are used in many diagnostic tests and are becoming increasingly important in the therapy of diseases. To express antibodies recombinantly, the immunoglobulin heavy and light chains are usually cloned into two different expression plasmids. Here, we describe a method for recombinant antibody expression from a single plasmid.
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Development of an antigen microarray for high throughput monoclonal antibody selection.
Biochem. Biophys. Res. Commun.
PUBLISHED: 01-25-2014
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Monoclonal antibodies are valuable laboratory reagents and are increasingly being exploited as therapeutics to treat a range of diseases. Selecting new monoclonal antibodies that are validated to work in particular applications, despite the availability of several different techniques, can be resource intensive with uncertain outcomes. To address this, we have developed an approach that enables early screening of hybridoma supernatants generated from an animal immunised with up to five different antigens followed by cloning of the antibody into a single expression plasmid. While this approach relieved the cellular cloning bottleneck and had the desirable ability to screen antibody function prior to cloning, the small volume of hybridoma supernatant available for screening limited the number of antigens for pooled immunisation. Here, we report the development of an antigen microarray that significantly reduces the volume of supernatant required for functional screening. This approach permits a significant increase in the number of antigens for parallel monoclonal antibody selection from a single animal. Finally, we show the successful use of a convenient small-scale transfection method to rapidly identify plasmids that encode functional cloned antibodies, addressing another bottleneck in this approach. In summary, we show that a hybrid approach of combining established hybridoma antibody technology with refined screening and antibody cloning methods can be used to select monoclonal antibodies of desired functional properties against many different antigens from a single immunised host.
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Induced multipotency in adult keratinocytes through down-regulation of ?Np63 or DGCR8.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-21-2014
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The roles of microRNAs (miRNAs) and the miRNA processing machinery in the regulation of stem cell biology are not well understood. Here, we show that the p53 family member and p63 isoform, ?Np63, is a transcriptional activator of a cofactor critical for miRNA processing (DGCR8). This regulation gives rise to a unique miRNA signature resulting in reprogramming cells to multipotency. Strikingly, ?Np63(-/-) epidermal cells display profound defects in terminal differentiation and express a subset of markers and miRNAs present in embryonic stem cells and fibroblasts induced to pluripotency using Yamanaka factors. Moreover, ?Np63(-/-) epidermal cells transduced with an inducible DGCR8 plasmid can differentiate into multiple cell fates in vitro and in vivo. We found that human primary keratinocytes depleted of ?Np63 or DGCR8 can be reprogrammed in 6 d and express a unique miRNA and gene expression signature that is similar but not identical to human induced pluripotent stem cells. Our data reveal a role for ?Np63 in the transcriptional regulation of DGCR8 to reprogram adult somatic cells into multipotent stem cells.
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Staging casual conversations for people with dementia.
Dementia (London)
PUBLISHED: 05-22-2013
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Social isolation is a key concern for individuals with dementia in long-term care. A possible solution is to promote social interaction between residents. A first step toward facilitating positive relationships between residents with dementia is to understand the mechanisms behind their interactions with each other, and also how their relationships with each other are built through such interactions. Drawing on casual conversations between residents in a special care unit for dementia, this paper uses systemic functional linguistics to examine how people with dementia use language to enact and construct their role-relations with each other. Results suggest people with dementia are able and willing conversationalists. However, factors such as the extent of communication breakdown and compatibility of the interlocutors may influence whether positive relations develop or not. Casual conversation is suggested to be a promising activity to encourage positive interpersonal processes between individuals with dementia in residential care.
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Contribution of cortical and white matter lesions to cognitive impairment in multiple sclerosis.
Mult. Scler.
PUBLISHED: 03-04-2013
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Cortical lesions (CLs) have been reported to be a better predictor for cognitive impairment than white matter (WM) lesions in relapsing-remitting multiple sclerosis (RRMS).
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Segments, letters and gestures: thoughts on doing and teaching phonetics and transcription.
Clin Linguist Phon
PUBLISHED: 11-24-2011
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This brief article reflects on some pitfalls inherent in the learning and teaching of segmental phonetic transcription. We suggest that a gestural interpretation to disordered speech data, in conjunction with segmental phonetic transcription, can add valuable insight into patterns of disordered speech, and that a gestural orientation should form part of the understanding and interpretation of the process of transcribing and the use of transcripts. We illustrate our discussion with data from a case of moderately to severely unintelligible speech produced by a boy aged 5;9.
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SMAC mimetic BV6 induces cell death in monocytes and maturation of monocyte-derived dendritic cells.
PLoS ONE
PUBLISHED: 06-03-2011
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Compounds mimicking the inhibitory effect of SMAC/DIABLO on X-linked inhibitor of apoptosis (XIAP) have been developed with the aim to achieve sensitization for apoptosis of tumor cells resistant due to deregulated XIAP expression. It turned out that SMAC mimetics also have complex effects on the NF?B system and TNF signaling. In view of the overwhelming importance of the NF?B transcription factors in the immune system, we analyzed here the effects of the SMAC mimetic BV6 on immune cells.
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Impaired ideomotor limb apraxia in cortical and subcortical dementia: a comparison of Alzheimers and Huntingtons disease.
Neurodegener Dis
PUBLISHED: 01-05-2011
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Although ideomotor limb apraxia is often considered to occur only in dementia with cortical involvement like Alzheimers disease (AD), it is also frequently seen in dementia with subcortical degeneration like Huntingtons disease (HD).
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The current Salmonella-host interactome.
Proteomics Clin Appl
PUBLISHED: 01-01-2011
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Salmonella bacteria cause millions of infections and thousands of deaths every year. This pathogen has an unusually broad host range including humans, animals, and even plants. During infection, Salmonella expresses a variety of virulence factors and effectors that are delivered into the host cell triggering cellular responses through protein-protein interactions (PPI) with host cell proteins which make the pathogens invasion and replication possible. To speed up proteomic efforts in elucidating Salmonella-host interactomes, we carried out a survey of the currently published Salmonella-host PPI. Such a list can serve as the gold standard for computational models aimed at predicting Salmonella-host interactomes through integration of large-scale biological data sources. Manual literature and database search of >2200 journal articles and >100 databases resulted in a gold standard list of currently 62 PPI, including primarily interactions of Salmonella proteins with human and mouse proteins. Only six of these interactions were directly retrievable from PPI databases and 16 were highlighted in databases featuring literature extracts. Thus, the literature survey resulted in the most complete interactome available to date for Salmonella. Pathway analysis using Ingenuity and Broad Gene Set Enrichment Analysis (GSEA) software revealed among general pathways such as MAPK signaling in particular those related to cell death as well as cell morphology, turnover, and interactions, in addition to response to not only Salmonella but also other pathogenic - viral and bacterial - infections. The list of interactions is available at http://www.shiprec.org/indicationslist.htm.
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Soluble and transmembrane TNF-like weak inducer of apoptosis differentially activate the classical and noncanonical NF-kappa B pathway.
J. Immunol.
PUBLISHED: 07-07-2010
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TNF-like weak inducer of apoptosis, TWEAK, is a typical member of the TNF ligand family. Thus, it is initially expressed as a type II transmembrane protein from which a soluble variant can be released by proteolytic processing. In this study, we show that membrane TWEAK is superior to soluble variant of TWEAK (sTWEAK) with respect to the activation of the classical NF-kappaB pathway, whereas both TWEAK variants are potent inducers of TNFR-associated factor-2 depletion, NF-kappaB-inducing kinase accumulation and p100 processing, hallmarks of activation of the noncanonical NF-kappaB pathway. Like other soluble TNF ligands with a poor capability to activate their corresponding receptor, sTWEAK acquires an activity resembling those of the transmembrane ligand by oligomerization or cell surface-immobilization. Blockade of the Fn14 receptor inhibited NF-kappaB signaling irrespective of the TWEAK form used for stimulation, indicating that the differential activities of the two TWEAK variants on classical and noncanonical NF-kappaB signaling is not related to the use of different receptors.
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Superior serum half life of albumin tagged TNF ligands.
Biochem. Biophys. Res. Commun.
PUBLISHED: 04-09-2010
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Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined by ELISA, was around 15 h as compared to approximately 1h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.
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Activation of transgenic estrogen receptor-beta by selected phytoestrogens in a stably transduced rat serotonergic cell line.
J. Steroid Biochem. Mol. Biol.
PUBLISHED: 03-15-2010
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Many flavonoids, a major group of phenolic plant-derived secondary metabolites, are known to possess estrogen-like bioactivities. However, little is known about their estrogenic properties in the central nervous system due to the lack of suitable cellular models expressing sufficient amounts of functional estrogen receptor beta (ERbeta). To overcome this deficit, we have created a cellular model, which is serotonergic in origin, to study properties of estrogenic substances by stably transducing RN46A-B14 cells derived from raphe nuclei region of the rat brain with a lentiviral vector encoding a human ERbeta. We clearly showed that the transgenic human ERbeta is a spontaneously expressed and a functional receptor. We have further assessed the estrogenicity of three different isoflavones and four different naringenin-type flavanones in this cell line utilizing a luciferase reporter gene assay. Genistein (GEN), Daidzein (DAI), Equol (EQ), Naringenin (NAR) and 8-prenylnaringenin (8-PN) showed strong estrogenic activity in a concentration-dependent manner as compared to 7-(O-prenyl)naringenin-4-acetate (7-O-PN) which was only slightly estrogenic and 6-(1,1-dimethylallyl)naringenin (6-DMAN) that neither showed estrogenic nor anti-estrogenic activity in our model. All observed effects could be antagonized by the anti-estrogen fulvestrant. Moreover, co-treatment of cells with 17beta-estradiol (E2) and either GEN or DAI showed a slight additive effect as compared to EQ. On the other hand, 8-PN in addition to 7-O-PN, but not NAR and 6-DMAN, were able to slightly antagonize the responses triggered by E2. Our newly established cellular model may prove to be a useful tool in explicating basic physiological properties of ERbeta in the brain and may help unravel molecular and cellular mechanisms involved in serotonergic mood regulation by estrogen or potential plant-derived secondary metabolites.
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Membrane tumor necrosis factor (TNF) induces p100 processing via TNF receptor-2 (TNFR2).
J. Biol. Chem.
PUBLISHED: 12-28-2009
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Tumor necrosis factor (TNF) elicits its biological activities by stimulation of two receptors, TNFR1 and TNFR2, both belonging to the TNF receptor superfamily. Whereas TNFR1-mediated signal transduction has been intensively studied and is understood in detail, especially with respect to activation of the classical NFkappaB pathway, cell death induction, and MAP kinase signaling, TNFR2-associated signal transduction is poorly defined. Here, we demonstrate in various tumor cell lines and primary T-cells that TNFR2, but not TNFR1, induces activation of the alternative NFkappaB pathway. In accord with earlier findings demonstrating that only membrane TNF, but not soluble TNF, properly activates TNFR2, we further show by use of TNFR1- and TNFR2-specific mutants of soluble TNF and membrane TNF that soluble ligand trimers fail to activate the alternative NFkappaB pathway. In accord with the known inhibitory role of TRAF2 in the alternative NFkappaB pathway, TNFR2-, but not TNFR1-specific TNF induced depletion of cytosolic TRAF2. Thus, we identified activation of the alternative NFkappaB pathway as a TNF signaling effect that can be specifically assigned to TNFR2 and membrane TNF.
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Oligomerized tumor necrosis factor-related apoptosis inducing ligand strongly induces cell death in myeloma cells, but also activates proinflammatory signaling pathways.
FEBS J.
PUBLISHED: 11-06-2009
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The oligomerization status of soluble tumor necrosis factor-related apoptosis inducing ligand (TRAIL) trimers has an overwhelming impact on cell death induction in a cell-type dependent fashion. Thus, we evaluated the ability of single and oligomerized TRAIL trimers to induce cell death in human myeloma cells. In all myeloma cell lines analyzed, oligomerized TRAIL trimers induced caspase activation and complete cell death, whereas non-oligomerized TRAIL trimers showed no or only a modest effect. Caspase activation induced by oligomerized TRAIL was blocked in all cell lines by the pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (z-VAD-fmk). Cell death induction was largely blocked in two cell lines by z-VAD-fmk, but was only marginally attenuated in three other cell lines, indicating that TRAIL induces caspase-dependent and caspase-independent cell death in myeloma cells. Preceding cell death, TRAIL activated nuclear factor kappaB, c-Jun N-terminal kinase, p38 and p42/44. Although TRAIL-induced stimulation of c-Jun N-terminal kinase and p38 was caspase-dependent in a cell type-specific fashion, activation of nuclear factor kappaB and p42/44 was caspase-independent in all cases. In accordance with activation of the nuclear factor kappaB pathway, we observed transcriptional up-regulation of several well established nuclear factor kappaB target genes. Furthermore, we found that TRAIL activates proinflammatory pathways in approximately 50% of primary myeloma samples. Taken together, our data suggest (a) that oligomerized TRAIL variants are necessary to ensure maximal cell death induction in myeloma cells and (b) TRAIL should be used in combination with anti-inflammatory drugs for treatment of myeloma to avoid and/or minimize any potential side-effects arising from the proinflammatory properties of the molecule.
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Discourses of dementia: a call for an ethnographic, action research approach to care in linguistically and culturally diverse environments.
Semin Speech Lang
PUBLISHED: 08-26-2009
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The methods of ethnography and action research have much to offer to the field of speech-language pathology, particularly as our clinical populations are becoming increasingly diverse. We suggest that practicing speech-language pathologists and students, as well as researchers, will benefit from strategies that use the methods of participatory action research and ethnography as guiding principles to their work. Ethnography seeks to discover meaningful structures in a culture from the perspective of those whose culture it is. Action research, which shares a methodological basis with ethnography, is undertaken with the aim of improving the functioning of the social institution, practice, or structure investigated for the benefit of those most closely involved with that institution or practice. By way of illustration, we use data collected during fieldwork in Louisiana, involving persons with dementia from linguistically and culturally diverse backgrounds.
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Aging with French: observations from South Louisiana.
J Cross Cult Gerontol
PUBLISHED: 08-19-2009
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South Louisiana is home to long-established French and French-Creole speaking minorities of varied origin. This paper reports on fieldwork observation in a nursing home among whose residents were many French speakers. The research question with which this context was approached was kept deliberately wide, namely, how bilingualism might feature in the lives of participants, or what the linguistic practices and preferences of participants might be. Thus, rather than impose pre-determined analytical categories on the research situation that could be formulated into a hypothesis to be tested by quantificational means, the work reported here is an attempt to describe the participants practices, and perspectives on the phenomenon under investigation.
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Trimer stabilization, oligomerization, and antibody-mediated cell surface immobilization improve the activity of soluble trimers of CD27L, CD40L, 41BBL, and glucocorticoid-induced TNF receptor ligand.
J. Immunol.
PUBLISHED: 07-13-2009
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For many ligands of the TNF family, trimer stability and oligomerization status are crucial determinants of receptor activation. However, for the immunostimulatory ligands CD27L, CD40L, 41BBL, and glucocorticoid-induced TNF receptor ligand (GITRL) detailed information regarding these requirements is lacking. Here, we comprehensively evaluated the effect of trimer stability and oligomerization on receptor activation by these ligands. Treatment with soluble Flag-tagged CD27L, 41BBL, and GITRL minimally activated receptor signaling, while Flag-CD40L was highly active. Oligomerization with anti-Flag Abs further enhanced the specific activity of Flag-CD40L 10-fold and of Flag-41BBL more than 200-fold, but it failed to activate Flag-CD27L and Flag-GITRL. We next investigated the relevance of trimer stability by introducing the tenascin-C (TNC) trimerization domain, yielding stabilized Flag-TNC-ligand trimers. Oligomerization with anti-Flag Ab potently activated signaling by Flag-TNC-CD27L and Flag-TNC-GITRL and, albeit to a lesser extent, Flag-TNC-CD40L and Flag-TNC-41BBL. Forced hexamerization, by introducing an Ig Fc domain, revealed that hexameric derivatives of Flag-TNC-41BBL, Flag-CD40L, and Flag-TNC-GITRL all activate receptor signaling with high efficiency, whereas hexameric Flag-CD27L variant left inactive. Finally, we attempted to selectively activate receptor signaling on targeted cells, by using Ab fragment (single-chain fragment variable region, scFv)-ligand fusion proteins, an approach previously applied to other TNF ligands. Target cell surface Ag-selective activation was achieved for scFv-41BBL, scFv-CD40L, and scFv-GITRL, although the latter two displayed already significant activity toward Ag-negative cells. In conclusion, our data establish that trimeric CD40L is active, 41BBL requires hexamerization, GITRL requires trimer stabilization, and CD27L requires trimer stabilization and oligomerization. Furthermore, surface immobilization might be exploited to gain locally enhanced ligand activity.
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The importance of narrow phonetic transcription for highly unintelligible speech: some examples.
Logoped Phoniatr Vocol
PUBLISHED: 05-19-2009
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The importance of the use of narrow phonetic transcription in transcribing a variety of speech disorders is emphasized. This point is illustrated with clinical data from the authors own research. The examples used are the transcription of a severely disfluent client, a child with progressive hearing loss, repair sequences in dysarthric speakers, a child with idiosyncratic velar articulations, and an adult with progressive speech degeneration. The use of the extended International Phonetic Alphabet (IPA) for the transcription of disordered speech and the Voice Quality Symbols (VoQS) system for transcribing voice quality is introduced and illustrated in the examples provided. The need for training in narrow transcription is discussed as part of a combination of impressionistic and instrumental description techniques.
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A pilot study of the pleth variability index as an indicator of volume-responsive hypotension in newborn infants during surgery.
J Anesth
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The aim of this pilot study was to evaluate the diagnostic value of pleth variability index (PVI) to predict fluid responsiveness in newborn infants during surgery.
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Applying systemic functional linguistics to conversations with dementia: the linguistic construction of relationships between participants.
Semin Speech Lang
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Social isolation in dementia is a growing concern as the incidence and prevalence of dementing conditions is on the rise in many societies. Positive social interactions, which foster the construction and enactment of positive interpersonal relationships and therefore positive discursive identities, make an important contribution to emotional well-being. In this article, we investigate how two women diagnosed with dementia of the Alzheimers type use language to relate to each other and two visiting graduate students. We use Systemic Functional Linguistics as an analytical framework, specifically investigating the use of vocatives and naming, and conversational moves and exchanges.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.