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  • Linguistics  (105)
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  • 1
    Online Resource
    Online Resource
    SAGE Publications ; 1982
    In:  Journal of Learning Disabilities Vol. 15, No. 1 ( 1982-01), p. 8-14
    In: Journal of Learning Disabilities, SAGE Publications, Vol. 15, No. 1 ( 1982-01), p. 8-14
    Abstract: A comprehensive approach to assessment and treatment of severe developmental speech and language disorders is discussed based on clinical experience with 69 children between 2 1/2 and 7 years of age. Assessment involves the integration of many variables, including differentiation between linguistic competence versus performance, diagnosis, familial and environmental factors, and pragmatics. A framework is presented that distinguishes therapy goals from therapy styles. The three possible goals are elimination or alleviation of causal factors, increase of interpersonal language interaction, and treatment of specific linguistic problems. These goals can be achieved within the context of three possible therapy styles: structured formal therapy, directed stimulation in play, and free play. The decision regarding choice of goals and styles is based on an integrative assessment, with the result that the treatment plan is appropriately designed for each individual.
    Type of Medium: Online Resource
    ISSN: 0022-2194 , 1538-4780
    Language: English
    Publisher: SAGE Publications
    Publication Date: 1982
    detail.hit.zdb_id: 2077783-8
    SSG: 5,2
    SSG: 5,3
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  • 2
    Online Resource
    Online Resource
    JSTOR ; 1983
    In:  The German Quarterly Vol. 56, No. 2 ( 1983-03), p. 285-
    In: The German Quarterly, JSTOR, Vol. 56, No. 2 ( 1983-03), p. 285-
    Type of Medium: Online Resource
    ISSN: 0016-8831
    RVK:
    Language: Unknown
    Publisher: JSTOR
    Publication Date: 1983
    detail.hit.zdb_id: 2066373-0
    detail.hit.zdb_id: 207506-4
    SSG: 7,20
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  • 3
    In: The Modern Language Review, JSTOR, Vol. 62, No. 2 ( 1967-04), p. 362-
    Type of Medium: Online Resource
    ISSN: 0026-7937
    RVK:
    Language: Unknown
    Publisher: JSTOR
    Publication Date: 1967
    detail.hit.zdb_id: 2046590-7
    SSG: 7,12
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  • 4
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 106, No. 7 ( 2009-02-17), p. 2124-2129
    Abstract: The African Plio-Pleistocene hominins known as australopiths evolved a distinctive craniofacial morphology that traditionally has been viewed as a dietary adaptation for feeding on either small, hard objects or on large volumes of food. A historically influential interpretation of this morphology hypothesizes that loads applied to the premolars during feeding had a profound influence on the evolution of australopith craniofacial form. Here, we test this hypothesis using finite element analysis in conjunction with comparative, imaging, and experimental methods. We find that the facial skeleton of the Australopithecus type species, A. africanus , is well suited to withstand premolar loads. However, we suggest that the mastication of either small objects or large volumes of food is unlikely to fully explain the evolution of facial form in this species. Rather, key aspects of australopith craniofacial morphology are more likely to be related to the ingestion and initial preparation of large, mechanically protected food objects like large nuts and seeds. These foods may have broadened the diet of these hominins, possibly by being critical resources that australopiths relied on during periods when their preferred dietary items were in short supply. Our analysis reconciles apparent discrepancies between dietary reconstructions based on biomechanics, tooth morphology, and dental microwear.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2009
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
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  • 5
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 43, No. 2 ( 2023-01-11), p. 333-345
    Abstract: Hexanucleotide repeat expansion (HRE) within C9orf72 is the most common genetic cause of frontotemporal dementia (FTD). Thalamic atrophy occurs in both sporadic and familial FTD but is thought to distinctly affect HRE carriers. Separately, emerging evidence suggests widespread derepression of transposable elements (TEs) in the brain in several neurodegenerative diseases, including C9orf72 HRE-mediated FTD (C9-FTD). Whether TE activation can be measured in peripheral blood and how the reduction in peripheral C9orf72 expression observed in HRE carriers relates to atrophy and clinical impairment remain unknown. We used FreeSurfer software to assess the effects of C9orf72 HRE and clinical diagnosis ( n = 78 individuals, male and female) on atrophy of thalamic nuclei. We also generated a novel, human, whole-blood RNA-sequencing dataset to determine the relationships among peripheral C9orf72 expression, TE activation, thalamic atrophy, and clinical severity ( n = 114 individuals, male and female). We confirmed global thalamic atrophy and reduced C9orf72 expression in HRE carriers. Moreover, we identified disproportionate atrophy of the right mediodorsal lateral nucleus in HRE carriers and showed that C9orf72 expression associated with clinical severity, independent of thalamic atrophy. Strikingly, we found global peripheral activation of TEs, including the human endogenous LINE-1 element L1HS . L1HS levels were associated with atrophy of multiple pulvinar nuclei, a thalamic region implicated in C9-FTD. Integration of peripheral transcriptomic and neuroimaging data from human HRE carriers revealed atrophy of specific thalamic nuclei, demonstrated that C9orf72 levels relate to clinical severity, and identified marked derepression of TEs, including L1HS , which predicted atrophy of FTD-relevant thalamic nuclei. SIGNIFICANCE STATEMENT Pathogenic repeat expansion in C9orf72 is the most frequent genetic cause of FTD and amyotrophic lateral sclerosis (ALS; C9-FTD/ALS). The clinical, neuroimaging, and pathologic features of C9-FTD/ALS are well characterized, whereas the intersections of transcriptomic dysregulation and brain structure remain largely unexplored. Herein, we used a novel radiogenomic approach to examine the relationship between peripheral blood transcriptomics and thalamic atrophy, a neuroimaging feature disproportionately impacted in C9-FTD/ALS. We confirmed reduction of C9orf72 in blood and found broad dysregulation of transposable elements—genetic elements typically repressed in the human genome—in symptomatic C9orf72 expansion carriers, which associated with atrophy of thalamic nuclei relevant to FTD. C9orf72 expression was also associated with clinical severity, suggesting that peripheral C9orf72 levels capture disease-relevant information.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2023
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 6
    In: Journal of Voice, Elsevier BV, Vol. 35, No. 2 ( 2021-03), p. 170-171
    Type of Medium: Online Resource
    ISSN: 0892-1997
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2111437-7
    SSG: 7,11
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  • 7
    Online Resource
    Online Resource
    IOP Publishing ; 1988
    In:  Europhysics Letters (EPL) Vol. 6, No. 3 ( 1988-06-01), p. 277-282
    In: Europhysics Letters (EPL), IOP Publishing, Vol. 6, No. 3 ( 1988-06-01), p. 277-282
    Type of Medium: Online Resource
    ISSN: 0295-5075 , 1286-4854
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 1988
    detail.hit.zdb_id: 1465366-7
    detail.hit.zdb_id: 165776-8
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  • 8
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 375, No. 6580 ( 2022-02-04)
    Abstract: Dubbed “forever chemicals” because of their innate chemical stability, per- and polyfluoroalkyl substances (PFAS) have been found to be ubiquitous environmental contaminants, present from the far Arctic reaches of the planet to urban rainwater. Although public awareness of these compounds is still relatively new, PFAS have been manufactured for more than seven decades. Over that time, industrial uses of PFAS have extended to 〉 200 diverse applications of 〉 1400 individual PFAS, including fast-food containers, anti-staining fabrics, and fire-suppressing foams. These numerous applications are possible and continue to expand because the rapidly broadening development and manufacture of PFAS is creating a physiochemically diverse class of thousands of unique synthetic chemicals that are related by their use of highly stable perfluorinated carbon chains. As these products flow through their life cycle from production to disposal, PFAS can be released into the environment at each step and potentially be taken up by biota, but largely migrating to the oceans and marine sediments in the long term. Bioaccumulation in both aquatic and terrestrial species has been widely observed, and while large-scale monitoring studies have been implemented, the adverse outcomes to ecological and human health, particularly of replacement PFAS, remain largely unknown. Critically, because of the sheer number of PFAS, environmental discovery and characterization studies struggle to keep pace with the development and release of next-generation compounds. The rapid expansion of PFAS, combined with their complex environmental interactions, results in a patchwork of data. Whereas the oldest legacy compounds such as perfluoroalkylcarboxylic (PFCAs) and perfluoroalkanesulfonic (PFSAs) have known health impacts, more recently developed PFAS are poorly characterized, and many PFAS even lack defined chemical structures, much less known toxicological end points. ADVANCES Continued measurement of legacy and next-generation PFAS is critical to assessing their behavior in environmental matrices and improving our understanding of their fate and transport. Studies of well-characterized legacy compounds, such as PFCAs and PFSAs, aid in the elucidation of interactions between PFAS chemistries and realistic environmental heterogeneities (e.g., pH, temperature, mineral assemblages, and co-contaminants). However, the reliability of resulting predictions depends on the degree of similarity between the legacy and new compounds. Atmospheric transport has been shown to play an important role in global PFAS distribution and, after deposition, mobility within terrestrial settings decreases with increasing molecular weight, whereas bioaccumulation increases. PFAS degradation rates within anaerobic settings and within marine sediments sharply contrast those within aerobic soils, resulting in considerable variation in biotransformation potential and major terminal products in settings such as landfills, oceans, or soils. However, regardless of the degradation pathway, natural transformation of labile PFAS includes PFAS reaction products, resulting in deposition sites such as landfills serving as time-delayed sources. Thus, PFAS require more drastic, destructive remediation processes for contaminated matrices, including treatment of residuals such as granular activated carbon from drinking water remediation. Destructive thermal and nonthermal processes for PFAS are being piloted, but there is always a risk of forming yet more PFAS products by incomplete destruction. OUTLOOK Although great strides have been taken in recent decades in understanding the fate, mobility, toxicity, and remediation of PFAS, there are still considerable management concerns across the life cycle of these persistent chemicals. The study of emerging compounds is complicated by the confidential nature of many PFAS chemistries, manufacturing processes, industrial by-products, and applications. Furthermore, the diversity and complexity of affected media are difficult to capture in laboratory studies. Unquestionably, it remains a priority for environmental scientists to understand behavior trends of PFAS and to work collaboratively with global regulatory agencies and industry toward effective environmental exposure mitigation strategies. The PFAS life cycle. PFAS product flows from primary producer to commercial user to consumers to disposal. Each step is attended by atmospheric and aqueous fugitive releases. Soils constitute a long-term environmental sink, slowly releasing PFAS to the hydrosphere and allowing uptake in biota, but the ultimate reservoir is deep marine sediment.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
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    detail.hit.zdb_id: 2066996-3
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    SSG: 11
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  • 9
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 1991
    In:  Proceedings of the National Academy of Sciences Vol. 88, No. 14 ( 1991-07-15), p. 6333-6337
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 88, No. 14 ( 1991-07-15), p. 6333-6337
    Abstract: Classification of humans as rapid or slow acetylators is based on hereditary differences in rates of N-acetylation of therapeutic and carcinogenic agents, but N-acetylation of certain arylamine drugs displays no genetic variations. Two highly homologous human genes for N-acetyltransferase (NAT; arylamine acetyltransferase, acetyl CoA:arylamine N-acetyltransferase, EC 2.3.1.5), NAT1 and NAT2, presumably code for the genetically invariant and variant NAT proteins, respectively. In the present investigation, 1.9-kilobase human genomic EcoRI fragments encoding NAT2 were generated by the polymerase chain reaction with liver and leukocyte DNA from seven subjects phenotyped as homozygous and heterozygous acetylators. Direct sequencing revealed multiple point mutations in the coding region of two distinct NAT2 variants. One of these was derived from leukocytes of a slow acetylator and was distinguished by a silent mutation (codon 94) and a separate G----A transition (position 590) leading to replacement of Arg-197 by Gln; the mutated guanine was part of a CpG dinucleotide and a Taq I site. The second NAT2 variant originated from liver with low N-acetylation activity. It was characterized by three nucleotide transitions giving rise to a silent mutation (codon 161), accompanied by obliteration of the sole Kpn I site, and two amino acid substitutions: Thr for Ile (codon 114) and Arg for Lys (codon 268). Heterozygosity was detected in three NAT2 samples: two were heterozygous for the rapid and one of the allelic variants, and the third was a compound heterozygote of both mutant alleles. The results show conclusively that the genetically variant NAT is encoded by NAT2.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1991
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 1988
    In:  Proceedings of the National Academy of Sciences Vol. 85, No. 20 ( 1988-10), p. 7709-7713
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 85, No. 20 ( 1988-10), p. 7709-7713
    Abstract: Analogs of interleukin 2 containing defined amino acid substitutions and deletions were assayed for bioactivity and for competitive binding to the high-affinity human interleukin 2 receptor complex and its two component subunits, a 55-kDa subunit (p55 or TAC) and a 70-kDa subunit (p70). Substitution of Asp20 or deletion of Phe124 resulted in inactive analog proteins that were unable to interact with the high-affinity p55/p70 complex or the intermediate-affinity p70 subunit of the interleukin 2 receptor. These analogs, however, retained the capacity to compete for binding to the low-affinity p55 subunit. The presence of the carboxylic acid in the side chain of Asp20 was necessary for effective binding to the p70 protein. In contrast, substitution of Trp121 and Leu17 created analogs that were inactive in the bioassay and all three binding assays. The effects of these mutations on protein conformation were assessed by circular dichroism. These results demonstrate that specific residues in the NH2 and COOH termini of interleukin 2 are crucial for its structure and activity.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1988
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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