Auditory Processing of Intonational Rises and Falls in German: Rises Are Special in Attention Orienting.

This article investigates the processing of intonational rises and falls when presented unexpectedly in a stream of repetitive auditory stimuli. It examines the neurophysiological correlates (ERPs) of attention to these unexpected stimuli through the use of an oddball paradigm where sequences of repetitive stimuli are occasionally interspersed with a deviant stimulus, allowing for elicitation of an MMN. Whereas previous oddball studies on attention toward unexpected sounds involving pitch rises were conducted on nonlinguistic stimuli, the present study uses as stimuli lexical items in German with naturalistic intonation contours. Results indicate that rising intonation plays a special role in attention orienting at a pre-attentive processing stage, whereas contextual meaning (here a list of items) is essential for activating attentional resources at a conscious processing stage. This is reflected in the activation of distinct brain responses: Rising intonation evokes the largest MMN, whereas falling intonation elicits a less pronounced MMN followed by a P3 (reflecting a conscious processing stage). Subsequently, we also find a complex interplay between the phonological status (i.e., accent/head marking vs. boundary/edge marking) and the direction of pitch change in their contribution to attention orienting: Attention is not oriented necessarily toward a specific position in prosodic structure (head or edge). Rather, we find that the intonation contour itself and the appropriateness of the contour in the linguistic context are the primary cues to two core mechanisms of attention orienting, pre-attentive and conscious orientation respectively, whereas the phonological status of the pitch event plays only a supplementary role.

The social and spiritual dimensions of parental experiences on end-of-life care of their child with cancer: A narrative review.

OBJECTIVE: Having a child with cancer is a burdensome experience for parents. Nurses need to better understand beliefs, hopes, and values of parents to holistically support them, which may have an impact on grief and depression. Thus, the aim of this paper was to highlight the social and spiritual dimensions of parental experiences on end-of-life care of their child with cancer. METHOD: A narrative literature review was conducted by systematically searching databases (CINAHL Complete, Academic Search Elite, MEDLINE) for relevant literature. The contents of included studies were critically appraised regarding their methodological quality. RESULTS: Eleven studies were included. In terms of the social dimension, three categories emerged that are important for parents: Being a Parent, Being in Relationship with the Child, and Being in Relationship with Health Professionals. Parents tried to maintain normality and joy for their child, but also kept control over the situation. They wanted to protect their child from suffering but also felt the need to talk to them about dying. Parents had ambivalent experiences with helpful but also burdensome staff. The spiritual dimension comprised two main categories, Hope and Faith and a Unique Bond. Hope was found to be an important source of strength, while Faith was only mentioned by some parents. For parents the emotional connection with their child constituted a source of meaning as well as a foundation, on which they based their decisions on. SIGNIFICANCE OF RESULTS: A therapeutic relationship and a supportive environment can be established by healthcare professionals by noticing, encouraging the unique bond between parents and their children, as well as by reflecting and addressing the parents' challenging situation.

Anaphoric Pronouns and the Computation of Prominence Profiles.

Previous research has investigated anaphoric resolution at the anaphor. Using a self-paced reading study we show that prominence profiles, i.e. the ranking of the referential candidates for anaphoric resolution, are dynamically established as discourse unfolds. We compared four types of context sentences introducing two referents and found that the cost of the computation of the prominence profile depends on the alignment of prominence-lending features, namely 'left edge', 'agent', 'subject'. Cost occurs as referents become available. Further downstream, we contrasted two types of pronouns in German, personal pronoun vs. demonstrative pronoun. By the time the pronoun is encountered, profile computation is already complete, as indicated by the lack of interaction between context and pronoun type. An effect of pronoun reveals that resolution is driven by the form-dependent strength with which an interpretation is obtained (demonstrative pronouns being more stable than personal pronouns). The results also indicate that two prominence-lending features - subjecthood and agentivity - compete with each other.

Agreement in Risk of Bias Assessment Between RobotReviewer and Human Reviewers: An Evaluation Study on Randomised Controlled Trials in Nursing-Related Cochrane Reviews.

PURPOSE: RobotReviewer is a machine learning system for semi-automated assistance in risk of bias assessment. The tools's performance in randomized controlled trials (RCTs) in the field of nursing remains unknown. We aimed therefore to evaluate the agreement in risk of bias assessment between RobotReviewer and human reviewers. DESIGN: Evaluation study using a retrospective diagnostic design. METHODS: We used RobotReviewer as the index test and human reviewers' risk of bias assessment reported in Cochrane reviews as the reference test. A convenience sample of electronically available English-language full texts of RCTs included in Cochrane reviews with nurs* in the title were eligible for inclusion. In this context, we assessed random sequence generation, allocation concealment, and blinding (personnel or participants and assessors) corresponding to Cochrane risk of bias version 2011. Two independent research teams performed and double-checked data extraction and analysis. We calculated sensitivity, specificity, receiver operating characteristic (ROC) curve, the area under the ROC curve, predictive values, observed percentage of agreement, and Cohen's kappa (including confidence intervals, if applicable). FINDINGS: The selection process yielded 190 RCTs published between 1958 and 2016 in 23 Cochrane reviews published between 2000 and 2018. Missing assessments of risk of bias domains in Cochrane reviews or RobotReviewer yielded varying sample sizes per risk of bias domain. Sensitivity ranged from 0.44 to 0.88 and specificity from 0.48 to 0.95. Positive predictive value was highest for allocation concealment (0.79) and lowest for blinding assessors (0.25). Cohen's kappa was moderate for randomization (0.52), allocation concealment (0.60), and for blinding of personnel/patients (0.43). Blinding of outcome assessors had only slight agreement (0.04). CONCLUSIONS: This is the first evaluation of risk of bias assessment by RobotReviewer in RCTs included in nursing-related Cochrane reviews. It yielded a moderate degree of agreement with human reviewers for randomization and allocation concealment, and an adequate sensitivity for detecting low risk of selection bias. CLINICAL RELEVANCE: Based on our results, using the RobotReviewer for risk of bias assessment in RCTs can be supportive in some risk of bias domains. However, human reviewers should supervise the semi-automated assessment process.

Cell death-inducing properties of selected dendrimers against different breast cancer and leukemia cell lines.

Dendrimers represent an opportunity for targeted drug delivery into tumor cells. This is facilitated, for example, by loading of dendrimers with anticancer compounds. However, to assess the effects caused by such conjugates, knowledge of the cytotoxicity of the dendrimers themselves is necessary. The poly(amido amine)-derived dendrimers G1 (Phe)6 , G1 (Dan)3 , and G2 were selected due to their different numbers of free amino groups and the poly(propylene imine) (PPI) dendrimer PPI-G3 served as a reference. The compounds were evaluated for cell-death induction using breast cancer (MCF-7, MDA-MB-231) and leukemia (LAMA-84, K562, SD-1, SUP-B15) cell lines. The compounds exhibited concentration-dependent effects in the low micromolar range against the mammary carcinoma cells. A dependency on the generation, and particularly on the type of dendrimer, was deduced while the quantity of the free amino groups was subsidiary. G2 revealed to be most cytotoxic, also against all tested leukemia cell lines. The cell line SD-1, however, was susceptible to all dendrimers. The mode of cell death was mainly determined by necrosis, especially at higher concentrations, while apoptosis played a subordinate role. The other dendrimers exerted no antimetabolic effects against LAMA-84, K562, and SUP-B15 cells. Therefore, these dendrimers are generally suitable as nontoxic drug carriers for leukemia cells.

The effect of Therapeutic Touch on Back Pain in Adults on a Neurological Unit: An Experimental Pilot Study.

BACKGROUND: Chronic back pain affects many aspects of everyday life and is a common reason for medical visits, leading to high direct and indirect health care costs. Innovative and cost-effective nonpharmacologic pain management methods should be promoted to ensure adequate treatment. AIMS: The aim of this pilot study was to investigate the pain-relieving effect of Therapeutic Touch in adult neurologic patients with back pain. DESIGN: A pretest-post-test randomized controlled trial. SETTINGS: A university hospital in Austria. PARTICIPANTS/SUBJECTS: Patients with back pain diagnosis (N = 29) on hospital admission. METHODS: A pilot study was conducted for 3 months. The control group (n = 14) received the pharmacologic pain management recommended by the World Health Organization; patients in the intervention group (n = 15) received additionally four Therapeutic Touch treatments on 4 consecutive days. The Quebec Back Pain Disability Scale and the Numeric Pain Rating Scale were used as outcome measures to evaluate activity domains affected by back pain and pain intensity. RESULTS: Pain improvement was found in the intervention group according to the mean score of the Quebec Back Pain Disability Scale (day 1: 72.53, standard deviation [SD] ± 14.10; day 4: 39.47, SD ± 8.77; p < .001). The Numerical Pain Rating Scale score averaged 4.33 points (SD ± 2.09) on the first day and 2.47 points (SD ± 1.12) on the fourth day. The long-term effect of Therapeutic Touch was significant and indicated a major effect (Pillai's trace = .641, F(3.12) = 7.1, p = .005, ηp2 = .641). CONCLUSIONS: Therapeutic Touch seems to be a noninvasive nursing intervention for back pain management to provide more professional patient care.

Care quality instruments.

PURPOSE: The purpose of this paper is to describe instruments used for quality assessment in acute care. Quality care assessment is essential for improving care delivery. Quality instruments can be used to evaluate nurse and patient perspectives in multi-professional care. Therefore, valid and reliable measurement instruments are vital. DESIGN/METHODOLOGY/APPROACH: A literature search identified several instruments that measure quality from a nurse and patient perspectives. The questionnaires were appraised in several steps with specific criteria: psychometric properties, underlying construct or test theory, study context, sample characteristics and target population. FINDINGS: Overall, 14 instruments were evaluated, but only eight questionnaires represented nurse and patient views regarding quality. Instruments showed several disparities in their theoretical foundations and their psychometric properties. Two instruments did not provide validity data and one questionnaire did not report reliability data. PRACTICAL IMPLICATIONS: To inform healthcare managers about acute care quality, the authors demonstrated the need for more valid and reliable measurements by using the Guidelines for Critiquing Instrument Development and Validation Reports to evaluate quality care instruments' psychometric properties. ORIGINALITY/VALUE: There is a long tradition in quality care evaluations using questionnaires. Only a few instruments can be recommended for practical use.

What naturalistic stimuli tell us about pronoun resolution in real-time processing.

Studies on pronoun resolution have mostly utilized short texts consisting of a context and a target sentence. In the current study we presented participants with nine chapters of an audio book while recording their EEG to investigate the real-time resolution of personal and demonstrative pronouns in a more naturalistic setting. The annotation of the features of the pronouns and their antecedents registered a surprising pattern: demonstrative pronouns showed an interpretive preference for subject/agent antecedents, although they are described to have an anti-subject or anti-agent preference. Given the presence of perspectival centers in the audio book, this however confirmed proposals that demonstrative pronouns are sensitive to perspectival centers. The ERP results revealed a biphasic N400-Late Positivity pattern at posterior electrodes for the demonstrative pronoun relative to the personal pronoun, thereby confirming previous findings with highly controlled stimuli. We take the observed N400 for the demonstrative pronoun as an indication for more demanding processing costs that occur due to the relative unexpectedness of this referential expression. The Late Positivity is taken to reflect the consequences of attentional reorientation: since the demonstrative pronoun indicates a possible shift in the discourse structure, it induces updating of the discourse structure. In addition to the biphasic pattern, the data showed an enhanced positivity at frontal electrode sites for the demonstrative pronoun relative to the personal pronoun. We suggest that this frontal positivity reflects self-relevant engagement and identification with the perspective holder. Our study suggests that by using naturalistic stimuli, we get one step closer to understanding the implementation of language processing in the brain during real life language processing.

Tracking meaning evolution in the brain: Processing consequences of conventionalization.

Language users employ creative and innovative means to refer to novel concepts. One example is place-for-event metonymy as in "How many bands played at Woodstock?" where the place name is used to refer to an event. We capitalize on the observation that place-for-event metonymy can on the one hand result in the conventionalization of the event reading (as is the case for "Woodstock") but on the other hand can also be relatively short-lived as a function of the socio-cultural or historical impact of the respective event (e.g., "Egypt" to refer to one of the sites of the Arab Spring). We use place-for-event metonymy as a test case to tap into discrete stages of conventionalization and compare the processing of the place and the event reading of particular expressions, with ratings of the degree of conventionalization as predictors. In an event-related potential (ERP) reading study, we observed a modulation of the Late Positivity between 500 and 750 ms post-onset by condition (event vs. place reading) and degree of conventionalization. The amplitude of the positivity was most pronounced for event readings with a low degree of conventionalization (similar to previous findings from ad-hoc metonymy). Interestingly, place readings with a high degree of (event) conventionalization also evoked a pronounced positivity. The Late Positivity is viewed to reflect processing demands during reconceptualization required for proper utterance interpretation. Overall, the data suggest that stages of meaning evolution are reflected in the underlying neurophysiological processes.

13C tracer analysis reveals the landscape of metabolic checkpoints in human CD8+ T cell differentiation and exhaustion.

Introduction: Naïve T cells remain in an actively maintained state of quiescence until activation by antigenic signals, upon which they start to proliferate and generate effector cells to initiate a functional immune response. Metabolic reprogramming is essential to meet the biosynthetic demands of the differentiation process, and failure to do so can promote the development of hypofunctional exhausted T cells. Methods: Here we used 13C metabolomics and transcriptomics to study the metabolism of CD8+ T cells in their complete course of differentiation from naïve over stem-like memory to effector cells and in exhaustion-inducing conditions. Results: The quiescence of naïve T cells was evident in a profound suppression of glucose oxidation and a decreased expression of ENO1, downstream of which no glycolytic flux was detectable. Moreover, TCA cycle activity was low in naïve T cells and associated with a downregulation of SDH subunits. Upon stimulation and exit from quiescence, the initiation of cell growth and proliferation was accompanied by differential expression of metabolic enzymes and metabolic reprogramming towards aerobic glycolysis with high rates of nutrient uptake, respiration and lactate production. High flux in anabolic pathways imposed a strain on NADH homeostasis, which coincided with engagement of the proline cycle for mitochondrial redox shuttling. With acquisition of effector functions, cells increasingly relied on glycolysis as opposed to oxidative phosphorylation, which was, however, not linked to changes in mitochondrial abundance. In exhaustion, decreased effector function concurred with a reduction in mitochondrial metabolism, glycolysis and amino acid import, and an upregulation of quiescence-associated genes, TXNIP and KLF2, and the T cell suppressive metabolites succinate and itaconate. Discussion: Overall, these results identify multiple metabolic features that regulate quiescence, proliferation and effector function, but also exhaustion of CD8+ T cells during differentiation. Thus, targeting these metabolic checkpoints may be a promising therapeutic strategy for both prevention of exhaustion and promotion of stemness of anti-tumor T cells.

(De-)accentuation and the process of information status: evidence from event-related brain potentials.

The paper reports on a perception experiment in German that investigated the neuro-cognitive processing of information structural concepts and their prosodic marking using event-related brain potentials (ERPs). Experimental conditions controlled the information status (given vs. new) of referring and non-referring target expressions (nouns vs. adjectives) and were elicited via context sentences, which did not - unlike most previous ERP studies in the field--trigger an explicit focus expectation. Target utterances displayed prosodic realizations of the critical words which differed in accent position and accent type. Electrophysiological results showed an effect of information status, maximally distributed over posterior sites, displaying a biphasic N400--Late Positivity pattern for new information. We claim that this pattern reflects increased processing demands associated with new information, with the N400 indicating enhanced costs from linking information with the previous discourse and the Late Positivity indicating the listener's effort to update his/her discourse model. The prosodic manipulation registered more pronounced effects over anterior regions and revealed an enhanced negativity followed by a Late Positivity for deaccentuation, probably also reflecting costs from discourse linking and updating respectively. The data further lend indirect support for the idea that givenness applies not only to referents but also to non-referential expressions ('lexical givenness').

Effects of metal salophene and saldach complexes on lymphoma and leukemia cells.

Schiff base transition metal complexes are an important class of compounds with great potential for therapeutic interventions. However, data on antileukemic and antilymphoma effects of these complexes are limited. The activity of N,N'-bis(salicylidene)-1,2-phenylenediamine (salophene, 1), its iron(II/III) and manganese(II/III) complexes as well as rac-trans-N,N'-bis(salicylidene)-1,2-cyclohexanediamine (saldach, 2) and its respective iron(II/III) complexes was evaluated against U-937 non-Hodgkin's lymphoma and the HL-60, SUP-B15, and K-562 leukemia cell lines. The free ligands induced in all cell lines, if at all, only marginal, concentration-dependent growth inhibitory effects, and did not trigger Cu/Zn superoxide dismutase (Cu/Zn SOD) release or induce apoptosis. [Fe(II) (salophene)] (3) and [Fe(III) (salophene)Cl] (4) blocked cellular growth, caused a strong release of Cu/Zn SOD and induced apoptosis. In contrast, the manganese analogs [Mn(II) (salophene)] (5) and [Mn(III) (salophene)OAc] (6) inhibited cell growth, caused the programmed cell death only at higher concentrations and did not provoke release of Cu/Zn SOD in any of the four cell lines. Weaker cell death-promoting effects were observed when the salophene moiety of 3 and 4 was replaced with saldach (complexes 7 and 8), indicating the influence exerted by the ligand structure. In conclusion, Schiff base transition metal complexes induce strong inhibitory effects on human lymphoma and leukemia cells.

Referential Chains Reveal Predictive Processes and Form-to-Function Mapping: An Electroencephalographic Study Using Naturalistic Story Stimuli.

In discourse pragmatics, different referential forms are claimed to be indicative of the cognitive status of a referent in the current discourse. Referential expressions thereby possess a double function: They point back to an (existing) referent (form-to-function mapping), and they are used to derive predictions about a referent's subsequent recurrence in discourse. Existing event-related potential (ERP) research has mainly focused on the form-to-function mapping of referential expression. In the present ERP study, we explore the relationship of form-to-function mapping and prediction derived from the antecedent of referential expressions in naturalistic auditory language comprehension. Specifically, the study investigates the relationship between the form of a referential expression (pronoun vs. noun) and the form of its antecedent (pronoun vs. noun); i.e., it examines the influence of the interplay of predictions derived from an antecedent (forward-looking function) and the form-to-function mapping of an anaphor (backward-looking function) on the ERPs time-locked to anaphoric expressions. The results in the time range of the P300 and N400 allow for a dissociation of these two functions during online language comprehension.

It is not always a matter of time: Addressing the costs of metaphor and metonymy through a speed-accuracy trade-off study.

One of the most debated topics in figurative language studies is whether the access to non-literal meanings is direct or indirect. Although models that argue for longer processing times for figurative compared to literal meanings have been largely criticized, figurative language is often associated with increased cognitive work. We investigated whether such greater cognitive work is indicative of more time-consuming processes or rather lower availability of figurative meanings, and whether there are differences between figurative types. We used a multi-response Speed-Accuracy Trade-off paradigm, where a meaningfulness judgment task was combined with a response deadline procedure to estimate speed and accuracy independently for metaphorical (Those dancers are butterflies) and metonymic sentences (That student reads Camilleri), compared with literal equivalents. While both metaphors and metonymies showed lower asymptote, that is, they were judged less accurately than literal counterparts, only metonymies were associated with a processing delay. Moreover, the difference in asymptote with respect to the literal condition was greater for metaphor than for metonymy. These findings indicate that the process that derives metaphor and metonymy is more complex than the process that derives literal meanings, even more so for metaphor. The processing delay, however, is present only in the case of metonymies. Taken together, our study offers key findings that reconcile a lively debate on the time course of figurative language comprehension, showing that the cost of non-literal meaning is not always a matter of time, and depends also on the figurative type. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A Bayesian Approach to German Personal and Demonstrative Pronouns.

When faced with an ambiguous pronoun, an addressee must interpret it by identifying a suitable referent. It has been proposed that the interpretation of pronouns can be captured using Bayes' Rule: P(referent|pronoun) ∝ P(pronoun|referent)P(referent). This approach has been successful in English and Mandarin Chinese. In this study, we further the cross-linguistic evidence for the Bayesian model by applying it to German personal and demonstrative pronouns, and provide novel quantitative support for the model by assessing model performance in a Bayesian statistical framework that allows implementation of a fully hierarchical structure, providing the most conservative estimates of uncertainty. Data from two story-continuation experiments showed that the Bayesian model overall made more accurate predictions for pronoun interpretation than production and next-mention biases separately. Furthermore, the model accounts for the demonstrative pronoun dieser as well as the personal pronoun, despite the demonstrative having different, and more rigid, resolution preferences.

The Cost of the Epistemic Step: Investigating Scalar Implicatures in Full and Partial Information Contexts.

We present the first ERP experiments that test the online processing of the scalar implicature some ⇝ not all in contexts where the speaker competence assumption is violated. Participants observe game scenarios with four open cards on the table and two closed cards outside of the table, while listening to statements made by a virtual player. In the full access context, the player makes a fully informed statement by referring only to the open cards, as cards on the table; in the partial access context, she makes a partially informed statement by referring to the whole set of cards, as cards in the game. If all of the open cards contain a given object X (Fullset condition), then some cards on the table contain Xs is inconsistent with the not all reading, whereas it is unknown whether some cards in the game contain X is consistent with this reading. If only a subset of the open cards contains X (Subset condition), then both utterances are known to be consistent with the not all implicature. Differential effects are observed depending on the quantifier reading adopted by the participant: For those participants who adopt the not all reading in the full access context, but not in the partial access context (weak pragmatic reading), a late posterior negativity effect is observed in the partial access context for the Fullset relative to the Subset condition. This effect is argued to reflect inference-driven context retrieval and monitoring processes related to epistemic reasoning involved in evaluating the competence assumption. By contrast, for participants who adopt the logical interpretation of some (some and possibly all), an N400 effect is observed in the partial access context, when comparing the Subset against the Fullset condition, which is argued to result from the competition between the two quantifying expressions some cards on the table and some cards in the game functioning in the experiment as scalar alternatives.

The role of missing killer cell immunoglobulin-like receptor ligands in T cell replete peripheral blood stem cell transplantation from HLA-identical siblings.

The contribution of natural killer (NK) cells to graft-versus-malignancy (GVM) effects following hematopoietic stem cell transplantation (HSCT) remains uncertain, particularly in the HLA-identical setting. A model considering missing HLA ligands to the donor's inhibitory killer cell immunoglobulin-like receptor (KIR), termed the missing KIR ligand model, has been established in T cell depleted bone marrow transplantation (BMT), but lacks validity in other cohorts with different treatment characteristics. We hypothesized that the impact of missing KIR ligands on relapse-free survival (RFS) and overall survival (OS) in T cell replete peripheral blood SCT (PBSCT) differs from that in the T cell depleted BMT setting, and retrospectively evaluated 100 consecutive, HLA-identical sibling transplantations for hematologic malignancies. In addition to KIR ligand status, we considered the donors' activating KIRs and grafted NK, T, and CD34(+) cell doses. Our findings demonstrate noninferiority for OS (P = .005) and RFS (P = .002) for the heterozygous HLA-C group KIR ligand status (C1/2; n = 47) compared with patients missing either C1 or C2 (n = 53). Similarly, OS (P = .031) and RFS (P = .034) of Bw4-positive patients was noninferior to that of patients missing a Bw4 ligand to KIR3DL1. By multivariate analysis, C1/2 heterozygous patients had a favorable risk ratio (RR) for relapse (RR = 0.28; P = .003), RFS (RR = 0.56; P = .046), and acute graft-versus-host disease grade II-IV (RR = 0.36; P = .05). Following reduced-intensity conditioning (RIC), but not standard-intensity conditioning, myeloablative (MA) transplantation, a grafted NK cell dose above the median (3.4 x 10(7)/kg) was associated with a lower risk of relapse (RR = 0.57; P = .003) and improved survival (RR = 0.78; P = .03). Overall, our findings support a role for NK alloreactivity in HLA-identical HSCT, but argue against a favorable impact of missing KIR ligands in the given setting. We conclude that the mechanism favoring the missing KIR ligand constellation in T cell depleted BMT may not operate in T cell replete PBSCT. The reasons for this differential effect remain unresolved.

Attention allocation in a language with post-focal prominences.

Accentuation influences selective attention and the depth of semantic processing during online speech comprehension. We investigated the processing of semantically congruent and incongruent words in a language that presents cues to prosodic prominences in the region of the utterance occurring after the focussed information (the post-focal region). This language is Italian, in particular the variety spoken in Bari. In this variety, questions have a compressed, post-focal accent, whereas in statements there is a low-level pitch in this position. Using event-related potentials, we investigated the processing of congruent and incongruent target words with two prosodic realizations (focussed with accentuation, post-focal realization) and in two-sentence modalities (statement, question). Results indicate an N400 congruence effect that was modulated by position (focal, post-focal) and modality (statement, question): processing was deeper for questions in narrow focus than in post-focal position, while statements showed similar pronounced N400 effects across positions. The attenuated N400 difference for post-focal targets in questions was accompanied by a more enhanced late positivity when they were incongruent, indicating that attentional resources are allocated during updating of speech act information.

Anti-leukemic activity of valproic acid and imatinib mesylate on human Ph+ ALL and CML cells in vitro.

The armamentarium of anti-leukemic drugs has increased substantially since anti-leukemic activities were recently found for a variety of non-classical cytostatic drugs, among them the histone deacetylase (HDAC) inhibitor valproic acid (VPA). This study investigated the effect of VPA on proliferation and apoptosis of human Philadelphia chromosome-positive (Ph+) acute lymphatic (ALL) and chronic myeloid leukemia (CML) cells and on colony formation of human chronic-phase CML progenitor cells. Strong anti-proliferative and pro-apoptotic effects of VPA were observed on human ALL and CML cell lines at concentrations achievable in vivo. These effects were most pronounced in ALL cell lines as well as in primary ALL cells. Notably, VPA revealed enhanced activity with imatinib mesylate, nilotinib, the farnesyl transferase inhibitor SCH66336, interferon-alpha and cytosine arabinoside. VPA inhibited the growth of colony-forming cells from 12 Ph+ chronic-phase CML patients but also of those from normal healthy controls in a dose-dependent fashion. HDAC-inhibiting activity of VPA was confirmed on ALL and CML cells. In conclusion, VPA, whether alone or in combination with other non-classical anti-leukemic compounds, exerts significant anti-leukemic effects on human ALL and CML cells.

Event-related potentials in pragmatic priming.

Priming of pragmatic enrichment has been found in behavioural studies. We extend this by examining the neural correlates of priming for two implicature categories, quantifiers and disjunctions. Participants engaged in a primed sentence-picture matching task where they were presented with a sentence (e.g., "some of the letters are Bs") followed by a picture. In prime trials the pictures were either consistent with an enriched interpretation (some but not all) or a basic interpretation (some and possibly all) of the sentence. The pictures in target trials were always consistent with the enriched interpretation. Using ERPs, we found a priming effect on the picture reflected in a reduced positivity for quantifiers when the preceding trial had an enriched interpretation, and no effect for disjunction. The pragmatic priming effect can be dissociated from expectation-based processes. It suggests that abstract derivation processes are primed during pragmatic alignment.