Effects of Massive Familiarization on Crossmodal Aesthetic Preference

An investigation was carried out to determine whether familiarization to the experience of visual dissonance would have crossmodal effects on the preference for dissonant and consonant musical stimuli. We hypothesized that subjects who viewed a large number of disharmonious color combinations would come to show greater liking for dissonant musical stimuli than their counterparts who had seen either harmonious or single color images. Findings showed that there was no difference in preference between groups, though musical experience and score on a benign masochism measure predicted larger differences between average ratings of consonant and dissonant chords. These results are discussed in light of prior findings regarding generalized preference variables and the short-term effects of a massive familiarization procedure

Reexamining the Effects of Ratio Simplicity and Familiarity on Abstract Pattern Learning in Dyad Sequences

In this study, we conceptually replicated two experiments by Crespo-Bojorque and Toro (2016; Experiments 4a & 5a) in an attempt to corroborate their finding of improved performance in abstract pattern learning within sequences of conventionally consonant versus dissonant dyads. In addition, to determine whether the processing advantages for consonance that they reported were due to the ratio simplicity or the familiarity of the stimuli, we added a condition in which participants were either presented with unconventionally tuned small versus large integer-ratio dyads. Results failed to replicate Crespo-Bojorque and Toro’s (2016) original findings: Neither conventionally consonant nor unconventionally tuned small integer-ratio dyads conferred any advantage in pattern learning or generalization. However, in a post hoc analysis using a subsample of participants with no music training, there was evidence that initial pattern learning was more efficient when the patterns were embedded within familiar as opposed to unconventionally tuned dyads. This is consistent with Crespo-Bojorque and Toro’s (2016) proposition that interval familiarity may bolster abstract pattern detection. Discussion centers on the need for additional research on the impact of consonance on pattern learning, highlighting the importance of adjudicating between the effects of ratio simplicity and enculturation

tofacitinib treatment is associated with modest and reversible increases in serum lipids in patients with ulcerative colitis

Background & Aims Tofacitinib is an oral, small-molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We analyzed inflammation, lipid concentrations, and incidence rates of major adverse cardiovascular (CV) events (MACEs) in patients who received tofacitinib in worldwide studies. Methods We collected data from 1157 patients who participated in 3 8-week induction studies (1 phase-2 study and 2 phase-3 studies; patients received tofacitinib 10 mg twice daily or placebo), a 52-week phase-3 maintenance study of responders (patients received tofacitinib 5 or 10 mg twice daily or placebo), and an ongoing long-term extension study of patients who did and did not respond to induction or maintenance therapy (patients received tofacitinib 5 or 10 mg twice daily). Lipid concentrations were assessed from induction baseline to week 61 (week 52 of maintenance therapy). We calculated MACE incidence rates (patients with ≥1 event per 100 patient-years of exposure) and Reynolds risk score (RRS; a composite score used to determine CV risk) for patients given tofacitinib vs placebo. Results The mean RRS was P Conclusions In an analysis of data from 5 trials of patients with UC who received tofacitinib, we found reversible increases in lipids with treatment and inverse correlations with reduced levels of high-sensitivity C-reactive protein. We did not find clinically meaningful changes in lipid ratios or RRS. MACEs were infrequent and not dose-related. Clinical trial registration Clinicaltrials.gov : A3921063 ( NCT00787202 ); OCTAVE Induction 1 ( NCT01465763 ); OCTAVE Induction 2 ( NCT01458951 ); OCTAVE Sustain ( NCT01458574 ); OCTAVE Open ( NCT01470612

Electromagnetic Weibel instability in intense charged particle beams with large energy anisotropy

In plasmas with strongly anisotropic distribution functions, collective instabilities may develop if there is sufficient coupling between the transverse and longitudinal degrees of freedom. Our previous numerical and theoretical studies of intense charged particle beams with large temperature anisotropy [E. A. Startsev, R. C. Davidson and H. Qin, PRSTAB, 6, 084401 (2003); Phys. Plasmas 9, 3138 (2002)] demonstrated that a fast, electrostatic, Harris-like instability develops, and saturates nonlinearly, for sufficiently large temperature anisotropy (T{sub {perpendicular}b}/T{sub {parallel}b} >> 1). The total distribution function after saturation, however, is still far from equipartitioned. In this paper the linearized Vlasov-Maxwell equations are used to investigate detailed properties of the transverse electromagnetic Weibel-type instability for a long charge bunch propagating through a cylindrical pipe of radius r{sub w}. The kinetic stability analysis is carried out for azimuthally symmetric perturbations about a two-temperature thermal equilibrium distribution in the smooth-focusing approximation. The most unstable modes are identified, and their eigenfrequencies, radial mode structure and instability thresholds are determined. The stability analysis shows that, although there is free energy available to drive the electromagnetic Weibel instability, the finite transverse geometry of the charged particle beam introduces a large threshold value for the temperature anisotropy ((T{sub {perpendicular}b}/T{sub {parallel}b}){sup Weibel} >> (T{sub {perpendicular}b}/T{sub {parallel}b}){sup Harris}) below which the instability is absent. Hence, unlike the case of an electrically neutral plasma, the Weibel instability is not expected to play as significant a role in the process of energy isotropization of intense unneutralized charged particle beams as the electrostatic Harris-type instability

Construction of gene regulatory networks using biclustering and bayesian networks

<p>Abstract</p> <p>Background</p> <p>Understanding gene interactions in complex living systems can be seen as the ultimate goal of the systems biology revolution. Hence, to elucidate disease ontology fully and to reduce the cost of drug development, gene regulatory networks (GRNs) have to be constructed. During the last decade, many GRN inference algorithms based on genome-wide data have been developed to unravel the complexity of gene regulation. Time series transcriptomic data measured by genome-wide DNA microarrays are traditionally used for GRN modelling. One of the major problems with microarrays is that a dataset consists of relatively few time points with respect to the large number of genes. Dimensionality is one of the interesting problems in GRN modelling.</p> <p>Results</p> <p>In this paper, we develop a biclustering function enrichment analysis toolbox (BicAT-plus) to study the effect of biclustering in reducing data dimensions. The network generated from our system was validated via available interaction databases and was compared with previous methods. The results revealed the performance of our proposed method.</p> <p>Conclusions</p> <p>Because of the sparse nature of GRNs, the results of biclustering techniques differ significantly from those of previous methods.</p

Reduction in downstream test utilization following introduction of coronary computed tomography in a cardiology practice

To compare utilization of non-invasive ischemic testing, invasive coronary angiography (ICA), and percutaneous coronary intervention (PCI) procedures before and after introduction of 64-slice multi-detector row coronary computed tomographic angiography (CCTA) in a large urban primary and consultative cardiology practice. We utilized a review of electronic medical records (NotesMD®) and the electronic practice management system (Megawest®) encompassing a 4-year period from 2004 to 2007 to determine the number of exercise treadmill (TME), supine bicycle exercise echocardiography (SBE), single photon emission computed tomography (SPECT) myocardial perfusion stress imaging (MPI), coronary calcium score (CCS), CCTA, ICA, and PCI procedures performed annually. Test utilization in the 2 years prior to and 2 years following availability of CCTA were compared. Over the 4-year period reviewed, the annual utilization of ICA decreased 45% (2,083 procedures in 2004 vs. 1,150 procedures in 2007, P < 0.01) and the percentage of ICA cases requiring PCI increased (19% in 2004 vs. 28% in 2007, P < 0.001). SPECT MPI decreased 19% (3,223 in 2004 vs. 2,614 in 2007 P < 0.02) and exercise stress treadmill testing decreased 49% (471 in 2004 vs. 241 in 2007 P < 0.02). Over the same period, there were no significant changes in measures of practice volume (office and hospital) or the annual incidence of PCI (405 cases in 2004 vs. 326 cases in 2007) but a higher percentage of patients with significant disease undergoing PCI 19% in 2004 vs. 29% in 2007 P < 0.01. Implementation of CCTA resulted in a significant decrease in ICA and a corresponding significant increase in the percentage of ICA cases requiring PCI, indicating that CCTA resulted in more accurate referral for ICA. The reduction in unnecessary ICA is associated with avoidance of potential morbidity and mortality associated with invasive diagnostic testing, reduction of downstream SPECT MPI and TME as well as substantial savings in health care dollars

Stringency of the 2-His–1-Asp Active-Site Motif in Prolyl 4-Hydroxylase

The non-heme iron(II) dioxygenase family of enzymes contain a common 2-His–1-carboxylate iron-binding motif. These enzymes catalyze a wide variety of oxidative reactions, such as the hydroxylation of aliphatic C–H bonds. Prolyl 4-hydroxylase (P4H) is an α-ketoglutarate-dependent iron(II) dioxygenase that catalyzes the post-translational hydroxylation of proline residues in protocollagen strands, stabilizing the ensuing triple helix. Human P4H residues His412, Asp414, and His483 have been identified as an iron-coordinating 2-His–1-carboxylate motif. Enzymes that catalyze oxidative halogenation do so by a mechanism similar to that of P4H. These halogenases retain the active-site histidine residues, but the carboxylate ligand is replaced with a halide ion. We replaced Asp414 of P4H with alanine (to mimic the active site of a halogenase) and with glycine. These substitutions do not, however, convert P4H into a halogenase. Moreover, the hydroxylase activity of D414A P4H cannot be rescued with small molecules. In addition, rearranging the two His and one Asp residues in the active site eliminates hydroxylase activity. Our results demonstrate a high stringency for the iron-binding residues in the P4H active site. We conclude that P4H, which catalyzes an especially demanding chemical transformation, is recalcitrant to change