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PubMed1999

Evidence for impaired sentence comprehension in early Alzheimer's disease.

We investigated sentence comprehension in 46 patients with probable minimal (very mild), mild, or moderate dementia of the Alzheimer type (DAT), comparing their performance on the Test for the Reception of Grammar (TROG), with that of 20 age- and education-matched controls. Performance on the TROG was generally related to dementia severity, independent of lexicosemantic and working memory (digit span) impairments, but related to at least 1 measure of attention. Some patients in the minimal group showed sentence comprehension deficits while others in the moderate group did not, indicating that DAT may impair sentence comprehension at the very earliest stages of disease, but that its effects are heterogeneous. Patients were most impaired on sentences with 2 propositions and noncanonical word order, suggesting difficulties with both interpretative and postinterpretative stages of sentence processing. Further investigation is needed into the relationship between attentional processes, interpretative and postinterpretative stages of syntactic processing in DAT.

Age Factors↗

PubMed2001

Objective data alignment and chemometric analysis of comprehensive two-dimensional separations with run-to-run peak shifting on both dimensions.

Data from comprehensive two-dimensional (2-D) separation techniques, such as comprehensive 2-D gas chromatography (GC x GC), liquid chromatography/liquid chromatography (LC x LC) and liquid chromatography/ capillary electrophoresis (LC x CE) can be readily analyzed by various chemometric methods to increase chemical analysis capabilities. A retention time alignment, preprocessing method is presented that objectively corrects for run-to-run retention time variations on both separation dimensions of comprehensive 2-D separations prior to application of chemometric data analysis algorithms. The 2-D alignment method corrects for run-to-run shifting of a sample data matrix relative to a standard data matrix on both separation time axes in an independent, stepwise fashion. After 2-D alignment, the generalized rank annihilation method (GRAM) is successfully applied, substantiating the performance of the alignment method. The alignment method should have important implications, because most 2-D separation techniques exhibit, in the context of chemometric data analysis, considerable run-to-run retention time shifting on both dimensions. Even when there are only three to four points/peak, that is, with three to four separations on the second dimension (column 2) per peak width from the first dimension (column 1), the 2-D alignment coupled with GRAM provides dependable analyte peak identification capabilities and adequate quantitative precision for unresolved analyte peaks. Thus, the 2-D alignment algorithm is applicable to lower data density conditions, which broadens the scope of chemometric analysis to high-speed 2-D separations.

Journal Article↗

PubMed2004

Simple and comprehensive two-dimensional reversed-phase HPLC using monolithic silica columns.

Simple and comprehensive two-dimensional (2D)-HPLC was studied in a reversed-phase mode using monolithic silica columns for second-dimension (2nd-D) separation. Every fraction from the first column, 15 cm long (4.6-mm i.d.), packed with fluoroalkylsilyl-bonded (FR) silica particles, was subjected to the separation in the 2nd-D using one or two octadecylsilylated (C(18)) monolithic silica columns (4.6-mm i.d., 3 cm). Monolithic silica columns in the 2nd-D were eluted at a flow rate of up to 10 mL/min with separation time of 30 s that meets the fractionation every 15-30 s at the first dimension (1st-D) operated at a flow rate of 0.4-0.8 mL/min. Three cases were studied. (1) In the simplest scheme of 2D-HPLC, effluent of the 1st-D was directly loaded into an injector loop of 2nd-D HPLC for 28 s, and 2 s was allowed for injection. (2) Two six-port valves each having a sample loop were used to hold the effluent of the 1st-D alternately for 30 s for one 2nd-D column to effect comprehensive 2D-HPLC without the loss of 1st-D effluent. (3) Two monolithic silica columns were used for 2nd-D by using a switching valve and two sets of 2nd-D chromatographs separating each fraction of the 1st-D effluent with the two 2nd-D columns alternately. In this case, two columns of the same stationary phase (C(18)) or different phases, C(18) and (pentabromobenzyloxy)propylsilyl-bonded (PBB), could be employed at the 2nd-D, although the latter needed two complementary runs. The systems produced peak capacity of approximately 1000 in approximately 60 min in cases 1 and 2 and in approximately 30 min in case 3. The three stationary phases, FR, C(18), and PBB, showed widely different selectivity from each other, making 2D separations possible. The simple and comprehensive 2D-HPLC utilizes the stability and high efficiency at high linear velocities of monolithic silica columns.

Journal Article↗

PubMed2006

Comprehensive gas chromatography-time-of-flight mass spectrometry using soft and selective photoionization techniques.

The hyphenation of gas chromatography and mass spectrometry (GC/MS) revolutionized organic analysis. In GC/MS coupling, usually electron impact ionization is applied, and molecules are identified by their fragment pattern. Although mass spectrometry in principle is a separation method, it is used predominantly as a spectrometric technique. However, if soft (i.e., fragmentation-free) ionization techniques are applied, the inherent separation character of MS is emphasized, which has similarities to a GC boiling point separation. By combining polar column GC separation and fast soft ionization time-of-flight mass spectrometry technology, a comprehensive separation of complex petrochemical samples can be obtained (GC x MS approach). Compounds of comparable physical-chemical properties are characteristically grouped together in a two-dimensional retention time-m/z representation. This resembles the separation characteristics of comprehensive two-dimensional gas chromatography (GC x GC) and, thus, represents a novel multidimensional separation approach. In this work, a gas chromatograph equipped with a polar separation column was coupled to a home-built laser ionization time-of-flight mass spectrometer. Laser-based, single-photon ionization was used for universal soft ionization and resonance-enhanced multiphoton ionization for selective ionization of aromatic compounds. A novel capillary-jet inlet system was used for the coupling. Multidimensional comprehensive analysis of complex petrochemical hydrocarbon samples using gas chromatography coupled to mass spectrometry with soft and selective photo ionization sources is first demonstrated.

Gas Chromatography-Mass Spectrometry↗

PubMed2006

Generating multiple independent retention index data in dual-secondary column comprehensive two-dimensional gas chromatography.

A method producing simultaneously three retention indexes for compounds has been developed for comprehensive two-dimensional gas chromatography by using a dual secondary column approach (GC x 2GC). For this purpose, the primary flow of the first dimension column was equally diverted into two secondary microbore columns of identical geometry by means of a three-way flow splitter positioned after the longitudinally modulated cryogenic system. This configuration produced a pair of comprehensive two-dimensional chromatograms and generated retention data on three different stationary phases in a single run. First dimension retention indexes were determined on a polar SolGel-Wax column under linear programmed-temperature conditions according to the van den Dool approach using primary alcohol homologues as the reference scale. Calculation of pseudoisothermal retention indexes in both second dimensions was performed on low-polarity 5% phenyl equivalent polysilphenylene/siloxane (BPX5) and 14% cyanopropylphenyl/86% dimethylpolysiloxane (BP10) columns. To construct a retention correlation map in the second dimension separation space upon which KovAts indexes can be derived, two methods exploiting "isovolatility" relationships of alkanes were developed. The first involved 15 sequential headspace samplings of selected n-alkanes by solid-phase microextraction (SPME), with each sampling followed by their injection into the GC at predetermined times during the chromatographic run. The second method extended the second dimension retention map and consisted of repetitive introduction of SPME-sampled alkane mixtures at various isothermal conditions incremented over the temperature program range. Calculated second dimension retention indexes were compared with experimental values obtained in conventional one-dimensional GC. A case study mixture including 24 suspected allergens (i.e., fragrance ingredients) was used to demonstrate the feasibility and potential of retention index information in comprehensive 2D-GC.

Journal Article↗

PubMed2001

Tethered processivity of the vitamin K-dependent carboxylase: factor IX is efficiently modified in a mechanism which distinguishes Gla's from Glu's and which accounts for comprehensive carboxylation in vivo.

The vitamin K-dependent (VKD) carboxylase binds VKD proteins via their propeptide and converts Glu's to gamma-carboxylated Glu's, or Gla's, in the Gla domain. Multiple carboxylation is required for activity, which could be achieved if the carboxylase is processive. In the only previous study to test for this capability, an indirect assay was used which suggested processivity; however, the efficiency was poor and raised questions regarding how full carboxylation is accomplished. To unequivocally determine if the carboxylase is processive and if it can account for comprehensive carboxylation in vivo, as well as to elucidate the enzyme mechanism, we developed a direct test for processivity. The in vitro carboxylation of a complex containing carboxylase and full-length factor IX (fIX) was challenged with an excess amount of a distinguishable fIX variant. Remarkably, carboxylation of fIX in the complex was completely unaffected by the challenge protein, and comprehensive carboxylation was achieved, showing conclusively that the carboxylase is processive and highly efficient. These studies also showed that carboxylation of individual fIX/carboxylase complexes was nonsynchronous and implicated a driving force for the reaction which requires the carboxylase to distinguish Glu's from Gla's. We found that the Gla domain is tightly associated with the carboxylase during carboxylation, blocking the access of a small peptide substrate (EEL). The studies describe the first analysis of preformed complexes, and the rate for full-length, native fIX in the complex was equivalent to that of the substrate EEL. Thus, intramolecular movement within the Gla domain to reposition new Glu's for catalysis is as rapid as diffusion-limited positioning of a small substrate, and the Gla domain is not sterically constrained by the rest of the fIX molecule during carboxylation. The rate of carboxylation of fIX in the preformed complex was 24-fold higher than for fIX modified by free carboxylase, which supports carboxylase processivity and which indicates that binding and/or release is the rate-limiting step in protein carboxylation. These data indicate a model of tethered processivity, in which the VKD proteins remain bound to the carboxylase throughout the reaction via their propeptide, while the Gla domain undergoes intramolecular movement to reposition new Glu's for catalysis to ultimately achieve comprehensive carboxylation.

Animals↗

PubMed2003

Comprehensive model for allosteric regulation of mammalian ribonucleotide reductase: refinements and consequences.

Reduction of NDPs by murine ribonucleotide reductase (mRR) requires catalytic (mR1) and free radical-containing (mR2) subunits and is regulated by nucleoside triphosphate allosteric effectors. Here we present the results of several studies that refine the recently presented comprehensive model for the allosteric control of mRR enzymatic activity [Kashlan, O. B., et al. (2002) Biochemistry 41, 462-474], in which nucleotide binding to the specificity site (s-site) drives formation of an active R1(2)R2(2) dimer, ATP or dATP binding to the adenine site (a-site) drives formation of a tetramer, mR1(4a), which isomerizes to an inactive form, mR1(4b), and ATP binding to the hexamerization site (h-site) drives formation of an active R1(6)R2(6) hexamer. Analysis of the a-site D57N variant of mR1, which differs from wild-type mR1 (wt-mR1) in that its RR activity is activated by both ATP and dATP, demonstrates that dATP activation of the D57N variant RR arises from a blockage in the formation of mR1(4b) from mR1(4a), and provides strong evidence that mR1(4a) forms active complexes with mR2(2). We further demonstrate that (a) differences in the effects of ATP versus dATP binding to the a-site of wt-mR1 provide specific mechanisms by which the dATP/ATP ratio in mammalian cells could modulate in vivo RR enzymatic activity, (b) the comprehensive model is valid over a range of Mg(2+) concentrations that include in vivo concentrations, and (c) equilibrium constants derived for the comprehensive model can be used to simulate the distribution of R1 among dimer, tetramer, and hexamer forms in vivo. Such simulations indicate that mR1(6) predominates over mR1(2) in the cytoplasm of normal mammalian cells, where the great majority of RR activity is located, but that mR1(2) may be important for nuclear RR activity and for RR activity in cells in which the level of ATP is depleted.

Adenosine Triphosphate↗

PubMed1997

Emotion, motivation, and text comprehension: the detection of contradictions in passages.

The authors investigated the effects of experimentally induced mood states on the identification of contradictions in text passages and ratings of comprehension in 3 experiments. Mood impaired comprehension in college students across a variety of passages, as evidenced by a depressive impairment in contradiction identification and an increased number of false identifications among depressed participants. Additionally, depressed individuals were less accurate in their judgments of passage difficulty. These findings are consistent with the resource allocation model of mood effects, which attributes impaired comprehension to the activation of intrusive, irrelevant thoughts during reading of the passage. It is further argued that these results cannot be explained simply by a deficit in motivation of the depressed participants.

Adult↗

PubMed1994

Communication in context: effects of speaker status on the comprehension of indirect requests.

Four experiments were conducted to examine how a speaker's status can affect the comprehension of conventional and nonconventional indirect requests. The processing of conventional forms was not affected by the speaker's relative status, and consistent with past research (R. W. Gibbs, 1983), these forms were recognized quickly and without the hearer recognizing and then rejecting the literal meaning of the remark. In contrast, processing of nonconventional forms was affected by speaker status. When the interactants were equal in status, the comprehension of nonconventional forms was time-consuming and involved activation of the remark's literal meaning. This did not occur when the speaker was higher in status than the hearer. Results illustrate the role played by the interpersonal context in the comprehension of certain indirect requests.

Cognition↗

PubMed1999

The comprehension and validation of social information.

The information one acquires in daily life concerns specific people and events about which one has prior knowledge. A theory of social cognition is proposed to account for the comprehension and verification of such information. The theory views comprehension as a process of constructing situation models of new information on the basis of previously formed models about its referents. The theory specifies the conditions in which statements about familiar people and events (e.g., "Jane Fonda does aerobics") are spontaneously recognized as true or false in the process of comprehending them. It further specifies the conditions in which these spontaneous validity judgments of a statement will influence perceptions of its implications when the statement is made in a social context. The comprehension of both single statements and multiple pieces of information in combination is considered.

Cognition↗

PubMed2006

The extended argument dependency model: a neurocognitive approach to sentence comprehension across languages.

Real-time language comprehension is a principal cognitive ability and thereby relates to central properties of the human cognitive architecture. Yet how do the presumably universal cognitive and neural substrates of language processing relate to the astounding diversity of human languages (over 5,000)? The authors present a neurocognitive model of online comprehension, the extended argument dependency model (eADM), that accounts for cross-linguistic unity and diversity in the processing of core constituents (verbs and arguments). The eADM postulates that core constituent processing proceeds in three hierarchically organized phases: (1) constituent structure building without relational interpretation, (2) argument role assignment via a restricted set of cross-linguistically motivated information types (e.g., case, animacy), and (3) completion of argument interpretation using information from further domains (e.g., discourse context, plausibility). This basic architecture is assumed to be universal, with cross-linguistic variation deriving primarily from the information types applied in Phase 2 of comprehension. This conception can derive the appearance of similar neurophysiological and neuroanatomical processing correlates in seemingly disparate structures in different languages and, conversely, of cross-linguistic differences in the processing of similar sentence structures.

Brain↗

PubMed1992

A capacity theory of comprehension: individual differences in working memory.

A theory of the way working memory capacity constrains comprehension is proposed. The theory proposes that both processing and storage are mediated by activation and that the total amount of activation available in working memory varies among individuals. Individual differences in working memory capacity for language can account for qualitative and quantitative differences among college-age adults in several aspects of language comprehension. One aspect is syntactic modularity: The larger capacity of some individuals permits interaction among syntactic and pragmatic information, so that their syntactic processes are not informationally encapsulated. Another aspect is syntactic ambiguity: The larger capacity of some individuals permits them to maintain multiple interpretations. The theory is instantiated as a production system model in which the amount of activation available to the model affects how it adapts to the transient computational and storage demands that occur in comprehension.

Concept Formation↗

PubMed2004

Using comprehensive feature lists to bias medical diagnosis.

Clinicians routinely report fewer features in a case than they subsequently agree are present. The authors report studies that assess the effect of considering a more comprehensive description than physicians usually offer. These comprehensive descriptions were generated from photographs of dermatology and internal medicine and were complete and accurate. Groups of clinicians of varying expertise were asked to offer a diagnosis based solely on the comprehensive verbal description. This initial exercise decreased the subsequent diagnostic acumen of experienced participants with the photographs relative to a group that initially diagnosed from the photographs. Reasons that the initial consideration of a list of features, all of which are present in the photograph, would decrease diagnostic accuracy are discussed.

Dermatology↗

PubMed2006

Is the right hemisphere involved in idiom comprehension? A neuropsychological study.

Nonambiguous idiom comprehension was assessed in 15 right brain-damaged (RBD) and 12 left brain-damaged (LBD) aphasic patients by means of a string-to-picture matching task. Idiom comprehension was found to be severely impaired with a bias toward literal interpretation. The RBD patients, though impaired, performed significantly better than LBD patients; their performance was correlated with visuospatial abilities and was significantly affected by lesion site. The results of this study suggest that the performance of RBD patients in the comprehension of idiomatic sentences may be affected by (a) an involvement of the frontal lobe and/or (b) visuospatial deficits that may impair their performance on the picture-matching task.

Adult↗

PubMed2002

Listening in aging adults: from discourse comprehension to psychoacoustics.

Older adults, whether or not they have clinically significant hearing loss, have more trouble than their younger counterparts understanding speech in everyday life. These age-related difficulties in speech understanding may be attributed to changes in higher-level cognitive processes such as language comprehension, memory, attention, and cognitive slowing, or to lower-level sensory and perceptual processes. A complicating factor in determining how these sources might contribute to age-related declines in speech understanding is that they are highly correlated. Experimenters have typically focused either on cognitive declines or sensory declines in artificially optimized test conditions. In contrast, our approach focuses on the complex interactions between age-related changes in cognitive and perceptual factors that affect spoken language comprehension, especially in nonideal, realistic conditions. In this article, we describe our attempts to systematically investigate sensory-cognitive interactions in controlled experimental situations. We begin by looking at experimental conditions that closely approximate everyday listening, and show that older adults do indeed experience deficits in spoken language comprehension relative to younger adults in these conditions. We then review further experiments designed to isolate more precisely the cognitive and perceptual sources of these age-related differences and how they vary with listening condition. In large part, we find that age-related changes in speech understanding are a consequence of auditory declines.

Aged↗

PubMedDate not supplied

A language-specific comprehension strategy.

Infants acquire whatever language is spoken in the environment into which they are born. The mental capability of the newborn child is not biased in any way towards the acquisition of one human language rather than another. Because psychologists who attempt to model the process of language comprehension are interested in the structure of the human mind, rather than in the properties of individual languages, strategies which they incorporate in their models are presumed to be universal, not language-specific. In other words, strategies of comprehension are presumed to be characteristic of the human language processing system, rather than, say, the French, English, or Igbo language processing systems. We report here, however, on a comprehension strategy which appears to be used by native speakers of French but not by native speakers of English.

Hearing↗

PubMed2006

Comprehensive volumetric optical microscopy in vivo.

Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects.

Angioplasty↗

PubMed2002

Balancing bilinguals II: lexical comprehension and cognitive processing in children learning Spanish and English.

The present study investigated developmental changes in lexical comprehension skills in early sequential bilinguals, in both Spanish (L1) and English (L2), exploring the effects of age, years of experience, and basic-level cognitive processing (specifically the ability to maintain performance during mixed vs. single-language processing) within a timed picture-word verification task. Participants were 100 individuals, 20 at each of five different age levels (ages in years, 5-7, 8-10, 11-13, 14-16, and adults). All had learned Spanish as a first language in the home, with formal English experience beginning at 5 years. Gains (as indexed by increased response speed) were made in both languages across age, although these gains were greater in English than in Spanish. The youngest participants were relatively "balanced" in their crosslinguistic performance. By middle childhood, performance was better in English. There were no response decrements at any age between the mixed and single-language processing conditions. These results are compared to those from a previous study that investigated basic-level lexical production in developing Spanish-English bilinguals. Both studies show a move toward English dominance in middle childhood, but the transition occurs earlier in comprehension. The production study showed differences between mixed and single-language processing (reflecting potential interlanguage interference) that are not evident in comprehension.

Adolescent↗