Miracle-dz/UniFAR-FTUs huggingface dataset:
Akt inhibitors induce apoptosis in chronic lymphocytic leukemia cells

Chronic lymphocytic leukemia (CLL) is now divisible into subsets with distinct clinical behaviors. The biology underlying these differences appears to include signaling pathways through the B-cell receptor and other receptors. The phosphatidylinositol-3-kinase/Akt pathway is important, raising the possibility that inhibitors could have therapeutic potential. Encouragingly, two inhibitors were found to induce preferential apoptosis of CLL cells, irrespective of TP53 status, with increases in NOXA and PUMA protein levels and a decrease in MCL-1. Background The phosphatidylinositol-3-kinase/Akt pathway has been described to be critical in the survival of chronic lymphocytic leukemia cells. In this study we analyzed the effect of two selective chemical inhibitors of Akt (Akti-1/2 and A-443654) on the survival of chronic lymphocytic leukemia cells. Design and Methods Using cytometry we studied the cytotoxic effects of Akt inhibitors on peripheral B and T lymphocytes from patients with chronic lymphocytic leukemia and from healthy donors. We studied the changes induced by Akti-1/2 and A-443654 at the mRNA level by performing reverse transcriptase multiplex ligation–dependent probe amplification. We also studied the changes induced by both Akt inhibitors in some BCL-2 protein family members on chronic lymphocytic leukemia cells by western blotting. Moreover, we analyzed the cytotoxic effect of Akt inhibitors in patients’ cells with deleted/mutated TP53. Results Both inhibitors induced apoptosis in chronic lymphocytic leukemia cells in a dose-dependent manner. Moreover, B cells from patients with chronic lymphocytic leukemia were more sensitive to Akt inhibitors than T cells from leukemic patients, and B or T cells from healthy donors. Survival factors for chronic lymphocytic leukemia cells, such as interleukin-4 and stromal cell-derived factor-1α, were not able to block the apoptosis induced by either Akt inhibitor. Akti-1/2 did not induce any change in the mRNA expression profile of genes involved in apoptosis, while A-443654 induced some changes, including an increase in NOXA and PUMA mRNA levels, suggesting the existence of additional targets for A-443654. Both inhibitors induced an increase in PUMA and NOXA protein levels, and a decrease in MCL-1 protein level. Moreover, Akti-1/2 and A-443654 induced apoptosis irrespective of TP53 status. Conclusions These results demonstrate that Akt inhibitors induce apoptosis of chronic lymphocytic leukemia cells and might be a new therapeutic option for the treatment of chronic lymphocytic leukemia.
Length scales, patterns and origin of azimuthal seismic anisotropy in the upper mantle as mapped by Rayleigh waves

SUMMARY We measure the degree of consistency between published models of azimuthal seismic anisotropy from surface waves, focusing on Rayleigh wave phase-velocity models. Some models agree up to wavelengths of ∼2000 km, albeit at small values of linear correlation coefficients. Others are, however, not well correlated at all, also with regard to isotropic structure. This points to differences in the underlying data sets and inversion strategies, particularly the relative ‘damping’ of mapped isotropic versus anisotropic anomalies. Yet, there is more agreement between published models than commonly held, encouraging further analysis. Employing a generalized spherical harmonic representation, we analyse power spectra of orientational (2� ) anisotropic heterogeneity from seismology. We find that the anisotropic component of some models is characterized by stronger short-wavelength power than the associated isotropic structure. This spectral signal is consistent with predictions from new geodynamic models, based on olivine texturing in mantle flow. The flow models are also successful in predicting some of the seismologically mapped patterns. We substantiate earlier findings that flow computations significantly outperform models of fast azimuths based on absolute plate velocities. Moreover, further evidence for the importance of active upwellings and downwellings as inferred from seismic tomography is presented. Deterministic estimates of expected anisotropic structure based on mantle flow computations such as ours can help guide future seismologic inversions, particularly in oceanic plate regions. We propose to consider such a priori information when addressing open questions about the averaging properties and resolution of surface and body wave based estimates of anisotropy.
Plasminogen activator-specific inhibitors produced by human monocytes/macrophages

Human monocytes/macrophages produce plasminogen activator-specific inhibitors (PAIs) that form covalent complexes with urokinase-type plasminogen activator (uPA). We have characterized two functionally and antigenically related forms of PAIs produced by resting and phorbol myristate acetate (PMA)-treated U 937 cells: an Mr 40,000 form, presumably nonglycosylated, with a pI of 5.2, that is constitutively synthetized by these cells and that remains predominantly intracellular; a PMA-induced form of heterogeneous Mr (50,000-65,000) with a pI of 4.7, that is preferentially secreted; this PAI is glycosylated with terminal sialic acid residue(s). Biosynthetic labeling experiments demonstrated that both PAIs are synthetized by U 937 cells. They are inactivated upon treatment with propanol, heat, and acid; the covalent and equimolar complexes formed between these PAIs and 125I-uPA are dissociated by ammonium hydroxide, suggesting that the PAIs are linked to uPA via an ester bond. Human peripheral blood monocytes/macrophages also produce the two forms of PAI. These PAIs are clearly different from the main plasma protease inhibitors and they are both antigenically related to the PAI-2 characterized in human placenta.
Surface Energy Balance Based Evapotranspiration Mapping in the Texas High Plains

Agriculture on the Texas High Plains (THP) uses approximately 89% of groundwater withdrawals from the Ogallala Aquifer. Consequently, groundwater levels are declining faster than the recharge rate. Therefore, efficient agricultural water use is essential for economic viability and sustainability of the THP. Accurate regional evapotranspiration (ET) maps would provide valuable information on actual crop water use. In this study, METRIC (Mapping Evapotranspiration at High Resolution using Internalized Calibration), a remote sensing based ET algorithm, was evaluated for mapping ET in the THP. Two Landsat 5 Thematic Mapper images acquired on 27 June (DOY 178) and 29 July (DOY 210) 2005 were used for this purpose. The performance of the ET model was evaluated by comparing the predicted daily ET with values derived from soil moisture budget at four commercial agricultural fields. Daily ET estimates resulted with a prediction error of 12.7±8.1% (mean bias error ± root mean square error) on DOY 178 and -4.7±9.4% on DOY 210 when compared with ET derived from measured soil moisture through the soil water balance. These results are good considering the prevailing advective conditions in the THP. METRIC have the potential to be used for mapping regional ET in the THP region. However, more evaluation is needed under different agroclimatological conditions.
A New Therapeutic Modality for Acute Myocardial Infarction: Nanoparticle-Mediated Delivery of Pitavastatin Induces Cardioprotection from Ischemia-Reperfusion Injury via Activation of PI3K/Akt Pathway and Anti-Inflammation in a Rat Model

Aim There is an unmet need to develop an innovative cardioprotective modality for acute myocardial infarction (AMI), for which the effectiveness of interventional reperfusion therapy is hampered by myocardial ischemia-reperfusion (IR) injury. Pretreatment with statins before ischemia is shown to reduce MI size in animals. However, no benefit was found in animals and patients with AMI when administered at the time of reperfusion, suggesting insufficient drug targeting into the IR myocardium. Here we tested the hypothesis that nanoparticle-mediated targeting of pitavastatin protects the heart from IR injury. Methods and Results In a rat IR model, poly(lactic acid/glycolic acid) (PLGA) nanoparticle incorporating FITC accumulated in the IR myocardium through enhanced vascular permeability, and in CD11b-positive leukocytes in the IR myocardium and peripheral blood after intravenous treatment. Intravenous treatment with PLGA nanoparticle containing pitavastatin (Pitavastatin-NP, 1 mg/kg) at reperfusion reduced MI size after 24 hours and ameliorated left ventricular dysfunction 4-week after reperfusion; by contrast, pitavastatin alone (as high as 10 mg/kg) showed no therapeutic effects. The therapeutic effects of Pitavastatin-NP were blunted by a PI3K inhibitor wortmannin, but not by a mitochondrial permeability transition pore inhibitor cyclosporine A. Pitavastatin-NP induced phosphorylation of Akt and GSK3β, and inhibited inflammation and cardiomyocyte apoptosis in the IR myocardium. Conclusions Nanoparticle-mediated targeting of pitavastatin induced cardioprotection from IR injury by activation of PI3K/Akt pathway and inhibition of inflammation and cardiomyocyte death in this model. This strategy can be developed as an innovative cardioprotective modality that may advance currently unsatisfactory reperfusion therapy for AMI.
Adoption of Mobile Commerce: A Confidence Model

This study was driven by three underlying motivations. One of them is the gap between high penetration rate of mobile phone and relatively low adoption rate of m-commerce. The second is to reconcile the inconsistent findings in prior IT adoption research regarding the consistency of the relationship between attitude and intention. Finally, we hope to provide the theoretical underpinning for various interventions to promote m-commerce adoption. In this study, we extended the theory of planned behavior (TPB) by integrating confidence as a moderator for the relationship between attitude and intention. Furthermore, trial, communication and observation are identified as the sources for confidence with m-commerce and their effects are mediated through exposure. The research model was empirically tested and supported. Both theoretical and practical implications are discussed.
Multimedia autoannotation via hierarchical semantic ensembles

This paper presents a hierarchical semantic ensemble learning method applied in the context of multimedia autoannotation. In contrast to the standard multiplecategory classification setting that assumes independent, non-overlapping and exhaustive set of categories, the proposed approach models explicitly the hierarchical relationships among target classes and estimates their relevance to a query as a trade-off between the goodness of fit to a given category description and its inherent uncertainty. The promising results of the empirical evaluation confirm the viability of the proposed approach, validated in comparison to several techniques of ensemble learning, as well as with different type of baseline classifiers.
Interactive mechanism modeling from multi-view images

In this paper, we present an interactive system for mechanism modeling from multi-view images. Its key feature is that the generated 3D mechanism models contain not only geometric shapes but also internal motion structures: they can be directly animated through kinematic simulation. Our system consists of two steps: interactive 3D modeling and stochastic motion parameter estimation. At the 3D modeling step, our system is designed to integrate the sparse 3D points reconstructed from multi-view images and a sketching interface to achieve accurate 3D modeling of a mechanism. To recover the motion parameters, we record a video clip of the mechanism motion and adopt stochastic optimization to recover its motion parameters by edge matching. Experimental results show that our system can achieve the 3D modeling of a range of mechanisms from simple mechanical toys to complex mechanism objects.
Evolution of crossmodal reorganization of the voice area in cochlear‐implanted deaf patients

Psychophysical and neuroimaging studies in both animal and human subjects have clearly demonstrated that cortical plasticity following sensory deprivation leads to a brain functional reorganization that favors the spared modalities. In postlingually deaf patients, the use of a cochlear implant (CI) allows a recovery of the auditory function, which will probably counteract the cortical crossmodal reorganization induced by hearing loss. To study the dynamics of such reversed crossmodal plasticity, we designed a longitudinal neuroimaging study involving the follow‐up of 10 postlingually deaf adult CI users engaged in a visual speechreading task. While speechreading activates Broca's area in normally hearing subjects (NHS), the activity level elicited in this region in CI patients is abnormally low and increases progressively with post‐implantation time. Furthermore, speechreading in CI patients induces abnormal crossmodal activations in right anterior regions of the superior temporal cortex normally devoted to processing human voice stimuli (temporal voice‐sensitive areas‐TVA). These abnormal activity levels diminish with post‐implantation time and tend towards the levels observed in NHS. First, our study revealed that the neuroplasticity after cochlear implantation involves not only auditory but also visual and audiovisual speech processing networks. Second, our results suggest that during deafness, the functional links between cortical regions specialized in face and voice processing are reallocated to support speech‐related visual processing through cross‐modal reorganization. Such reorganization allows a more efficient audiovisual integration of speech after cochlear implantation. These compensatory sensory strategies are later completed by the progressive restoration of the visuo‐audio‐motor speech processing loop, including Broca's area. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc
Genome-wide reorganization of histone H2AX toward particular fragile sites on cell activation

γH2AX formation by phosphorylation of the histone variant H2AX is the key process in the repair of DNA lesions including those arising at fragile sites under replication stress. Here we demonstrate that H2AX is dynamically reorganized to preoccupy γH2AX hotspots on increased replication stress by activated cell proliferation and that H2AX is enriched in aphidicolin-induced replisome stalling sites in cycling cells. Interestingly, H2AX enrichment was particularly found in genomic regions that replicate in early S phase. High transcription activity, a hallmark of early replicating fragile sites, was a determinant of H2AX localization. Subtelomeric H2AX enrichment was also attributable to early replication and high gene density. In contrast, late replicating and infrequently transcribed regions, including common fragile sites and heterochromatin, lacked H2AX enrichment. In particular, heterochromatin was inaccessible to H2AX incorporation, maybe partly explaining the cause of mutation accumulation in cancer heterochromatin. Meanwhile, H2AX in actively dividing cells was intimately colocalized with INO80. INO80 silencing reduced H2AX levels, particularly at the INO80-enriched sites. Our findings suggest that active DNA replication is accompanied with the specific localization of H2AX and INO80 for efficient damage repair or replication-fork stabilization in actively transcribed regions.
Ieee Transactions on Information Theory Co~tcluding Remarks

A class of codes, having check matrices which are the tensor products of the check matrices of nonbinary and binary codes has been described. In particular, it has been shown in detail how the error-correction, error-detection and error-location capabilities of such codes depend on the component codes. Many other variations of such codes exist in addition to those discussed in this paper. In some applications it may be desirable to have subblocks of various sizes. One of the most easily implemented means to this end would be to choose the code C' to yield the maximum desired subblock size and then delete columns of the check matrix H' corresponding to the desired " shorter " sub-blocks. (If C' is a cyclic code, shortened cyclic codes would be used for the shorter subblocks). Alternatively, C' can be replaced by a sequence of binary codes (each code for a separate subblock) all of which have p check digits but possibly have different lengths and error-control capabilities. Moreover, independent of the choice of block length other classes of error patterns in addition to random errors and single burst errors can be utilized for &i and G;'. For example, the process can be iterated to obtain codes for the correction of " bursts of bursts. of bursts. " A channel model in which errors occur in " bursts of bursts. of bursts " has been proposed by Mandelbrot
Got Replicability? The _Journal of Money, Credit and Banking_ Archive

In a paper published in the Journal of Money, Credit and Banking, McGeary, Harrison, and I showed that the JMCBâ€™s data+code archive of generally did not support the replication of the journalâ€™s published results. We recommended several procedures for ensuring that the archived data and code would reproduce the published results. The JMCB Editors recently adopted a few new procedures, ignoring most of the recommendations. This paper checks to see whether the new procedures are working. They are not.
Withdrawal from treatment as an outcome in the ISOLDE study of COPD.

OBJECTIVES To investigate the determinants of patient withdrawal from our study, and the effect of these withdrawals on the outcome of treatment with inhaled corticosteroids in patients with COPD. DESIGN A double-blind, placebo-controlled, randomized trial. SETTING Eighteen outpatient centers in the United Kingdom. PARTICIPANTS Seven hundred fifty-one patients with stable COPD defined clinically and as baseline postbronchodilator FEV(1) > or = 0.8 L and < 85% predicted, FEV(1)/FVC ratio < 70%, and FEV(1) change after albuterol < 10% of predicted. INTERVENTION Random assignment of either 500 microg bid of inhaled fluticasone propionate (FP) using a spacer device or an identical placebo inhaler. Treatment was continued for 3 years or until patients withdrew from follow-up. MEASUREMENTS AND RESULTS Postbronchodilator FEV(1) was measured on three occasions before randomization and every 3 months thereafter. Health status was assessed by the disease-specific St. George Respiratory Questionnaire (SGRQ) and the modified short-form 36 questionnaire (SF-36) at baseline and every 6 months. Three hundred thirty-nine patients withdrew, of whom 156 patients received FP. Prescription of frequent courses of oral prednisolone was the most common reason for withdrawing as specified in the protocol (69 patients in the FP group withdrew due to respiratory symptoms, compared with 93 patients in the placebo group). This explained the significantly greater dropout of placebo-treated patients that was most evident when FEV(1) was < 50% predicted. Patients withdrawing had a significantly more rapid decline in health status, measured by both the SGRQ and the SF-36 (p < 0.001). Those withdrawing from the placebo group had a more rapid decline in FEV(1) and more exacerbations than the FP-treated groups. Baseline FEV(1) was lower in dropouts than in patients completing the study receiving placebo, but there was no difference between the respective groups receiving FP. CONCLUSIONS Patients who withdrew from follow-up were those with the most rapidly deteriorating health status and lung function. Losing these patients from the final analysis can reduce the power of a study to achieve its primary end point.
Audit expectation gap: The case of Malaysia

Based on the studies by Schelluch and Best et al., this study aims to investigate the existence of an audit expectation gap in Malaysia. The main motivation comes from the lack of research on the issue since the Enron and Andersen debacles. Besides, the Malaysian accounting environment has significantly improved since the 1998s reform, with the passing of the Financial Reporting Act and the establishment of the Malaysian Accounting Standards Board. The results indicate wide expectation gaps and misconceptions about audit in Malaysia. An experiment conducted among investors revealed the effectiveness of the use of reading material to educate users and correcting some misconceptions.
Learning-Induced Physiological Memory in Adult Primary Auditory Cortex: Receptive Field Plasticity, Model, and Mechanisms

It is well established that the functional organization of adult sensory cortices, including the auditory cortex, can be modified by deafferentation, sensory deprivation, or selective sensory stimulation. This paper reviews evidence establishing that the adult primary auditory cortex develops physiological plasticity during learning. Determination of frequency receptive fields before and at various times following aversive classical conditioning and instrumental avoidance learning in the guinea pig reveals increased neuronal responses to the pure tone frequency used as a conditioned stimulus (CS). In contrast, responses to the pretraining best frequency and other non-CS frequencies are decreased. These opposite changes are often sufficient to shift cellular tuning toward or even to the frequency of the CS. Learning-induced receptive field (RF) plasticity (i) is associative (requires pairing tone and shock), (ii) highly specific to the CS frequency (e.g., limited to this frequency ± a small fraction of an octave), (iii) discriminative (specific increased response to a reinforced CS+ frequency but decreased response to a nonreinforced CS– frequency), (iv) develops extremely rapidly (within 5 trials, the fewest trials tested), and (v) is retained indefinitely (tested to 8 weeks). Moreover, RF plasticity is robust and not due to arousal, but can be expressed in the deeply anesthetized subject. Because learning- induced RF plasticity has the major characteristics of associative memory, it is therefore referred to as ‘physiological memory. ’ We developed a model of RF plasticity based on convergence in the auditory cortex of nucleus basalis cholinergic effects acting at muscarinic receptors, with lemniscal and nonlemniscal frequency information from the ventral and magnocellular divisions of the medial geniculate nucleus, respectively. In the model, the specificity of RF plasticity is dependent on Hebbian rules of covariance. This aspect was confirmed in vivo using microstimulation techniques. Further, the model predicts that pairing a tone with activation of the nucleus basalis is sufficient to induce RF plasticity similar to that obtained in behavioral learning. This prediction has been confirmed. Additional tests of the model are described. RF plasticity is thought to translate the acquired significance of sound into an increased frequency representation of behaviorally important stimuli.