Dual-modality impairment of implicit learning of letter-strings versus color-patterns in patients with schizophrenia

BACKGROUND: Implicit learning was reported to be intact in schizophrenia using artificial grammar learning. However, emerging evidence indicates that artificial grammar learning is not a unitary process. The authors used dual coding stimuli and schizophrenia clinical symptom dimensions to re-evaluate the effect of schizophrenia on various components of artificial grammar learning. METHODS: Letter string and color pattern artificial grammar learning performances were compared between 63 schizophrenic patients and 27 comparison subjects. Four symptom dimensions derived from a Chinese Positive and Negative Symptom Scale ratings were correlated with patients' artificial grammar implicit learning performances along the two stimulus dimensions. Patients' explicit memory performances were assessed by verbal paired associates and visual reproduction subtests of the Wechsler Memory Scales Revised Version to provide a contrast to their implicit memory function. RESULTS: Schizophrenia severely hindered color pattern artificial grammar learning while the disease affected lexical string artificial grammar learning to a lesser degree after correcting the influences from age, education and the performance of explicit memory function of both verbal and visual modalities. Both learning performances correlated significantly with the severity of patients' schizophrenic clinical symptom dimensions that reflect poor abstract thinking, disorganized thinking, and stereotyped thinking. CONCLUSION: The results of this study suggested that schizophrenia affects various mechanisms of artificial grammar learning differently. Implicit learning, knowledge acquisition in the absence of conscious awareness, is not entirely intact in patients with schizophrenia. Schizophrenia affects implicit learning through an impairment of the ability of making abstractions from rules and at least in part decreasing the capacity for perceptual learning

A General Phase Matching Condition for Quantum Searching Algorithm

A general consideration on the phase rotations in quantum searching algorithm is taken in this work. As four phase rotations on the initial state, the marked states, and the states orthogonal to them are taken account, we deduce a phase matching condition for a successful search. The optimal options for these phase are obtained consequently.Comment: 3 pages, 3 figure

A General SU(2) Formulation for Quantum Searching with Certainty

A general quantum search algorithm with arbitrary unitary transformations and an arbitrary initial state is considered in this work. To serach a marked state with certainty, we have derived, using an SU(2) representation: (1) the matching condition relating the phase rotations in the algorithm, (2) a concise formula for evaluating the required number of iterations for the search, and (3) the final state after the search, with a phase angle in its amplitude of unity modulus. Moreover, the optimal choices and modifications of the phase angles in the Grover kernel is also studied.Comment: 8 pages, 2 figure

Evaluation of an entraining droplet activation parameterization using in situ cloud data

This study investigates the ability of a droplet activation parameterization (which considers the effects of entrainment and mixing) to reproduce observed cloud droplet number concentration (CDNC) in ambient clouds. Predictions of the parameterization are compared against cloud averages of CDNC from ambient cumulus and stratocumulus clouds sampled during CRYSTAL‐FACE (Key West, Florida, July 2002) and CSTRIPE (Monterey, California, July 2003), respectively. The entrainment parameters required by the parameterization are derived from the observed liquid water content profiles. For the cumulus clouds considered in the study, CDNC is overpredicted by 45% with the adiabatic parameterization. When entrainment is accounted for, the predicted CDNC agrees within 3.5%. Cloud‐averaged CDNC for stratocumulus clouds is well captured when entrainment is not considered. In all cases considered, the entraining parameterization compared favorably against a statistical correlation developed from observations to treat entrainment effects on droplet number. These results suggest that including entrainment effects in the calculation of CDNC, as presented here, could address important overprediction biases associated with using adiabatic CDNC to represent cloud‐scale average values

Auditory Event-Related Potentials in Antipsychotic-Free Subjects With Ultra-High-Risk State and First-Episode Psychosis

Background: Auditory event-related potentials (ERPs) have been utilized to study defective information processing of patients with schizophrenia. To delineate the pathophysiological processes from pre-psychotic state to first-episode psychosis, a study on subjects from ultra-high-risk (UHR) state to first-episode psychosis, ideally in an antipsychotic-free condition, can add important information to our understanding.Methods: Patients with UHR state or at their first-episode psychosis (FEP) who were drug-naive or only have been temporarily treated with antipsychotics were assessed by auditory ERPs measurement, including P50/N100 (sensory gating) and duration mismatch negativity (MMN; deviance detection). A group of age-matched healthy subjects served as their controls.Results: A total of 42 patients (23 UHR and 19 FEP) and 120 control subjects were recruited, including 21 pure drug-naive and 21 with very short exposure to antipsychotics. Collapsing FEP and UHR as a patient group, they exhibited significant sensory deficits manifested as larger P50 S2 amplitude, larger N100 ratio, and smaller N100 difference, and significantly less deviance detection response revealed by MMN. Such differences were less significant when treating FEP and UHR separately for comparisons. Comparisons of ERP results between drug-naive subjects and antipsychotic-short-exposure subjects revealed no significant difference in any P50/N100 and MMN parameter.Conclusion: Our study is one of the few studies focused on drug-naive or minimally treated patients at pre- or early-psychotic states. Our results exhibited impaired performance in sensory gating and deviance detection shown by certain parameters. A longitudinal study with larger sample sizes will be helpful to provide more evidence to elucidate the role of antipsychotics on an individual’s neurophysiological performance at different stages of psychosis

Frequency Dependent Alterations in Regional Homogeneity of Baseline Brain Activity in Schizophrenia

Low frequency oscillations are essential in cognitive function impairment in schizophrenia. While functional connectivity can reveal the synchronization between distant brain regions, the regional abnormalities in task-independent baseline brain activity are less clear, especially in specific frequency bands. Here, we used a regional homogeneity (ReHo) method combined with resting-state functional magnetic resonance imaging to investigate low frequency spontaneous neural activity in the three different frequency bands (slow-5:0.01–0.027 Hz; slow-4:0.027–0.08 Hz; and typical band: 0.01–0.08 Hz) in 69 patients with schizophrenia and 62 healthy controls. Compared with controls, schizophrenia patients exhibited decreased ReHo in the precentral gyrus, middle occipital gyrus, and posterior insula, whereas increased ReHo in the medial prefrontal cortex and anterior insula. Significant differences in ReHo between the two bands were found in fusiform gyrus and superior frontal gyrus (slow-4> slow-5), and in basal ganglia, parahippocampus, and dorsal middle prefrontal gyrus (slow-5> slow-4). Importantly, we identified significant interaction between frequency bands and groups in the inferior occipital gyrus and caudate body. This study demonstrates that ReHo changes in schizophrenia are widespread and frequency dependent

High versus standard doses interferon-alpha in the treatment of naïve chronic hepatitis C patients in Taiwan: a 10-year cohort study

BACKGROUND: Interferon-alpha monotherapy is effective in less than one-third patients with chronic hepatitis C. The dose-effect, tolerability and durability of interferon-alpha treatment and its long-term effect on the prevention of cirrhosis and hepatocellular carcinoma in naïve Taiwanese patients with chronic hepatitis C have not been well investigated. We conducted the present cohort study treated with high and standard interferon-alpha to illustrate the issues. METHODS: We performed a long-term virologic and histological follow-up of 214 chronic hepatitis C patients treated with interferon-alpha, 3 million units (3-MU, n = 80) or 6-MU (n = 134) thrice weekly for 24 weeks, in Taiwan between 1992 and 2001. RESULTS: There was no difference in the incidence of discontinuation between 3-MU and 6-MU groups (4/80, 5.0% versus 10/134. 7.5%). The 6-MU group had similar incidence of adverse events with the 3-MU group, except that 6-MU group had significantly higher incidence of psychological manifestations, mainly presented as irritability. The rates of sustained virological response (SVR) were significantly higher in 6-MU regimen (37.1%) than in 3-MU regimen (23.7%, p < 0.05) in per protocol analysis. Based on multivariate analysis, baseline viral load was strongly associated with SVR, followed by hepatitis C virus genotype, interferon-alpha regimen, and liver fibrosis. A histological improvement in necroinflammatory activity, but not in fibrosis was observed in the follow-up biopsy performed 0.5–5.5 years (mean: 1.9 years, n = 51) after end-of-treatment. Among patients without SVR, there was more activity improvement in 6-MU group. The durability of SVR was 100% (18/18) and 97.8% (45/46) for 3-MU and 6-MU group, respectively, in a mean follow-up period of 6.81 years (5.25–9.18 years). For 163 baseline non-cirrhotic patients, 9 of 84 (10.7%) non-responders and 3 of 79 (3.8%) sustained responders progressed to cirrhosis during a mean follow-up period of 5.52 and 5.74 years, respectively (p = 0.067, Kaplan-Meier survival analysis, log-rank test). For all 200 patients, hepatocellular carcinoma was detected in 12 of 113 (10.6%) non-responders and one of 87 (1.1%) sustained responders during a mean follow-up period of 5.67 and 5.73 years, respectively (p < 0.01, Kaplan-Meier survival analysis, log-rank test). CONCLUSION: We confirm the dose effect of interferon-alpha in chronic hepatitis C. Six-MU regimen had better efficacy than 3-MU regimen in virologic and histological responses. Both regimens had good tolerability and durability in Taiwan. Sustained response could reduce the incidence of cirrhotic change and hepatocarcinogenesis

Women Under Kuomintang R ule Variations on the Feminine Mystique

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68360/2/10.1177_009770047500100101.pd

Re-expression of ARHI (DIRAS3) induces autophagy in breast cancer cells and enhances the inhibitory effect of paclitaxel

<p>Abstract</p> <p>Background</p> <p><it>ARHI </it>is a Ras-related imprinted gene that inhibits cancer cell growth and motility. ARHI is downregulated in the majority of breast cancers, and loss of its expression is associated with its progression from ductal carcinoma <it>in situ </it>(DCIS) to invasive disease. In ovarian cancer, re-expression of ARHI induces autophagy and leads to autophagic death in cell culture; however, ARHI re-expression enables ovarian cancer cells to remain dormant when they are grown in mice as xenografts. The purpose of this study is to examine whether ARHI induces autophagy in breast cancer cells and to evaluate the effects of ARHI gene re-expression in combination with paclitaxel.</p> <p>Methods</p> <p>Re-expression of ARHI was achieved by transfection, by treatment with trichostatin A (TSA) or by a combination of TSA and 5-aza-2'-deoxycytidine (DAC) in breast cancer cell cultures and by liposomal delivery of ARHI in breast tumor xenografts.</p> <p>Results</p> <p>ARHI re-expression induces autophagy in breast cancer cells, and ARHI is essential for the induction of autophagy. When ARHI was re-expressed in breast cancer cells treated with paclitaxel, the growth inhibitory effect of paclitaxel was enhanced in both the cell culture and the xenografts. Although paclitaxel alone did not induce autophagy in breast cancer cells, it enhanced ARHI-induced autophagy. Conversely, ARHI re-expression promoted paclitaxel-induced apoptosis and G2/M cell cycle arrest.</p> <p>Conclusions</p> <p>ARHI re-expression induces autophagic cell death in breast cancer cells and enhances the inhibitory effects of paclitaxel by promoting autophagy, apoptosis, and G2/M cell cycle arrest.</p

Mechanistic target of rapamycin (MTOR) protein expression in the tumor and its microenvironment correlates with more aggressive pathology at cystectomy

Background: The mechanistic target of rapamycin (mTOR) has been implicated in driving tumor biology in multiple malignancies, including urothelial carcinoma (UC). We investigate how mTOR and phosphorylated mTOR (pmTOR) protein expression correlate with chemoresponsiveness in the tumor and its microenvironment at final pathologic staging after neoadjuvant chemotherapy (NAC). Methods: A single-institution retrospective analysis was performed on 62 patients with cT2–4Nany UC undergoing NAC followed by radical cystectomy. Diagnostic (transurethral resection specimens, TURBT) and postchemotherapy radical cystectomy specimens were evaluated for mTOR and pmTOR protein expression using immunohistochemistry of the tumor, peritumoral stroma, and normal surrounding stroma. Protein expression levels were compared between clinical and pathologic stage. Whole transcriptome analysis was performed to evaluate mRNA expression relative to mTOR pathway activation. Results: Baseline levels of mTOR and pmTOR within TURBT specimens were not associated with clinical stage and response to chemotherapy overall. Nonresponders with advanced pathologic stage at cystectomy (ypT2–4/ypTanyN+) had significantly elevated mTOR tumor staining (P = 0.006) and a sustained mTOR and pmTOR staining in the peritumoral and surrounding normal stroma (NS). Several genes relevant to mTOR activity were found to be up-regulated in the tumors of nonresponders. Remarkably, complete responders at cystectomy (ypT0) had significant decreases in both mTOR and pmTOR protein expression in the peritumoral and normal stroma (P = 0.01–0.03). Conclusions: Our results suggest that mTOR pathway activity is increased in tumor and sustained in its microenvironment in patients with adverse pathologic findings at cystectomy. These findings suggest the relevance of targeting this pathway in bladder cancer