Dark Quest. I. Fast and Accurate Emulation of Halo Clustering Statistics and Its Application to Galaxy Clustering

We perform an ensemble of $N$-body simulations with $2048^3$ particles for 101 flat $w$CDM cosmological models sampled based on a maximin-distance Sliced Latin Hypercube Design. By using the halo catalogs extracted at multiple redshifts in the range of $z=[0,1.48]$, we develop Dark Emulator, which enables fast and accurate computations of the halo mass function, halo-matter cross-correlation, and halo auto-correlation as a function of halo masses, redshift, separations and cosmological models, based on the Principal Component Analysis and the Gaussian Process Regression for the large-dimensional input and output data vector. We assess the performance of the emulator using a validation set of $N$-body simulations that are not used in training the emulator. We show that, for typical halos hosting CMASS galaxies in the Sloan Digital Sky Survey, the emulator predicts the halo-matter cross correlation, relevant for galaxy-galaxy weak lensing, with an accuracy better than $2\%$ and the halo auto-correlation, relevant for galaxy clustering correlation, with an accuracy better than $4\%$. We give several demonstrations of the emulator. It can be used to study properties of halo mass density profiles such as the mass-concentration relation and splashback radius for different cosmologies. The emulator outputs can be combined with an analytical prescription of halo-galaxy connection such as the halo occupation distribution at the equation level, instead of using the mock catalogs, to make accurate predictions of galaxy clustering statistics such as the galaxy-galaxy weak lensing and the projected correlation function for any model within the $w$CDM cosmologies, in a few CPU seconds.Comment: 46 pages, 47 figures; version accepted for publication in Ap

Cortical Regions Encoding Hardness Perception Modulated by Visual Information Identified by Functional Magnetic Resonance Imaging With Multivoxel Pattern Analysis

Recent studies have revealed that hardness perception is determined by visual information along with the haptic input. This study investigated the cortical regions involved in hardness perception modulated by visual information using functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA). Twenty-two healthy participants were enrolled. They were required to place their left and right hands at the front and back, respectively, of a mirror attached to a platform placed above them while lying in a magnetic resonance scanner. In conditions SFT, MED, and HRD, one of three polyurethane foam pads of varying hardness (soft, medium, and hard, respectively) was presented to the left hand in a given trial, while only the medium pad was presented to the right hand in all trials. MED was defined as the control condition, because the visual and haptic information was congruent. During the scan, the participants were required to push the pad with the both hands while observing the reflection of the left hand and estimate the hardness of the pad perceived by the right (hidden) hand based on magnitude estimation. Behavioral results showed that the perceived hardness was significantly biased toward softer or harder in >73% of the trials in conditions SFT and HRD; we designated these trials as visually modulated (SFTvm and HRDvm, respectively). The accuracy map was calculated individually for each of the pair-wise comparisons of (SFTvm vs. MED), (HRDvm vs. MED), and (SFTvm vs. HRDvm) by a searchlight MVPA, and the cortical regions encoding the perceived hardness with visual modulation were identified by conjunction of the three accuracy maps in group analysis. The cluster was observed in the right sensory motor cortex, left anterior intraparietal sulcus (aIPS), bilateral parietal operculum (PO), and occipito-temporal cortex (OTC). Together with previous findings on such cortical regions, we conclude that the visual information of finger movements processed in the OTC may be integrated with haptic input in the left aIPS, and the subjective hardness perceived by the right hand with visual modulation may be processed in the cortical network between the left PO and aIPS

Effect of Visual Information on Active Touch During Mirror Visual Feedback

Several studies have demonstrated that observation of a dummy or mirror-reflected hand being stroked or moving at the same time as the hidden hand evokes a feeling that the dummy hand is one’s own, such as the rubber hand illusion (RHI) and mirror visual feedback (MVF). Under these conditions, participants also report sensing the tactile stimulation applied to the fake hands, suggesting that tactile perception is modulated by visual information during the RHI and MVF. Previous studies have utilized passive stimulation conditions; however, active touch is more common in real-world settings. Therefore, we investigated whether active touch is also modulated by visual information during an MVF scenario. Twenty-three participants (13 men and 10 women; mean age ± SD: 21.6 ± 2.0 years) were required to touch a polyurethane pad with both hands synchronously, and estimate the hardness of the pad while observing the mirror reflection. When participants observed the mirror reflection of the other hand pushing a softer or harder pad, perceived hardness estimates were significantly biased toward softer or harder, respectively, even though the physical hardness of the pad remained constant. Furthermore, perceived hardness exhibited a strong correlation with finger displacement of the mirrored, but not hidden, hand. The modulatory effects on perceived hardness diminished when participants touched the pad with both hands asynchronously or with their eyes closed. Moreover, participants experienced ownership of the mirrored hand when they touched the pad with both hands synchronously but not asynchronously. These results indicate that hardness estimates were modulated by observation of the mirrored hand during synchronous touch conditions. The present study demonstrates that, similar to passive touch, active touch is also modulated by visual input

Structural Basis of the Highly Efficient Trapping of the HIV Tat Protein by an RNA Aptamer

AbstractAn RNA aptamer containing two binding sites exhibits extremely high affinity to the HIV Tat protein. We have determined the structure of the aptamer complexed with two argininamide molecules. Two adjacent U:A:U base triples were formed, which widens the major groove to make space for the two argininamide molecules. The argininamide molecules bind to the G bases through hydrogen bonds. The binding is stabilized through stacking interactions. The structure of the aptamer complexed with a Tat-derived arginine-rich peptide was also characterized. It was suggested that the aptamer structure is similar for both complexes and that the aptamer interacts with two different arginine residues of the peptide simultaneously at the two binding sites, which could explain the high affinity to Tat

Hormonal Therapy Resistant Estrogen-receptor Positive Metastatic Breast Cancer Cohort (HORSE-BC) Study : Current Status of Treatment Selection in Japan

The Hormonal therapy resistant estrogen-receptor positive metastatic breast cancer cohort (HORSE-BC) study is a multicenter observational study evaluating the efficacy and safety of secondary endocrine therapy (ET) for postmenopausal cases of metastatic breast cancer (MBC) with poor response to primary ET. In this initial report we analyze the HORSE-BC baseline data to clarify the current status of treatment selection for MBC in Japan. Baseline data for the 50 patients enrolled in HORSE-BC were analyzed, including patient characteristics, types of secondary ET, and reasons for selecting secondary ET. Postoperative recurrence was detected in 84% of patients (42/50) and de novo stage IV breast cancer in 16% (8/50). Forty-one patients (41/50; 82%) received fulvestrant, 5 patients (10%) received selective estrogen receptor modulators (SERMs), 3 patients (6%) received ET plus a mammalian target of rapamycin (mTOR) inhibitor, and 1 patient received an aromatase inhibitor (AI) as the secondary ET. Forty-five patients selected their secondary ET based on its therapeutic effect, while 14 patients selected it based on side effects. Most patients with progression after primary ET selected fulvestrant as the secondary ET based on its therapeutic and side effects. We await the final results from the HORSE-BC study

Randomized phase II study to determine the optimal dose of 3-week cycle nab-paclitaxel in patients with metastatic breast cancer

Background Chemotherapy-induced peripheral neuropathy is commonly observed in patients treated with nanoparticle albumin–bound paclitaxel (nab-PTX). We conducted a multicenter randomized controlled study to evaluate the optimal dose of nab-PTX. Methods We compared three different doses of q3w nab-PTX (Standard: 260 mg/m2 [SD260] vs Medium: 220 mg/m2 [MD220] vs Low: 180 mg/m2 [LD180]) in patients with HER2-negative metastatic breast cancer (MBC). Primary endpoint was progression-free survival (PFS). Grade 3/4 neuropathy rates in the three doses were estimated using the logistic regression model. The optimal dose was selected in two steps. Initially, if the hazard ratio (HR) for PFS was 1.33, the inferior dose was excluded, and we proceeded with the non-inferior dose. Then, if the estimated incidence rate of grade 3/4 neurotoxicity exceeded 10%, that dose was also excluded. Results One hundred forty-one patients were randomly assigned to SD260 (n = 47), MD220 (n = 46), and LD180 (n = 48) groups, and their median PFS was 6.66, 7.34, and 6.82 months, respectively. The HRs were 0.73 (95% confidence interval [CI]: 0.42–1.28) in MD220 vs SD260, 0.77 (95% CI 0.47–1.28) in LD180 vs SD260, and 0.96 (95% CI 0.56–1.66) in LD180 vs MD220. SD260 was inferior to MD220 and was excluded. The estimated incidence rate of grade 3/4 neurotoxicity was 29.5% in SD260, 14.0% in MD220, and 5.9% in LD180. The final selected dose was LD180. Conclusions Intravenous administration of low-dose nab-PTX at 180 mg/m2 q3w may be the optimal therapy with meaningful efficacy and favorable toxicity in patients with MBC

Association of Genetic Polymorphism with Taxane-induced Peripheral Neuropathy: Sub-analysis of a Randomized Phase II Study to Determine the Optimal Dose of 3-week Cycle Nab-Paclitaxel in Metastatic Breast Cancer Patients

Chemotherapy-induced peripheral neuropathy (CIPN) is an important clinical challenge that threatens patients’ quality of life. This sub-study of the ABROAD trial investigated the influence of single nucleotide polymorphisms (SNPs) on CIPN, using genotype data from a randomized study to determine the optimal dose of a 3-week-cycle regimen of nab-paclitaxel (q3w nab-PTX) in patients with metastatic breast cancer (MBC). Patients with HER2-negative MBC were randomly assigned to three doses of q3w nab-PTX (SD: 260 mg/m2 vs. MD: 220 mg/m2 vs. LD: 180 mg/m2). Five SNPs (EPHA4-rs17348202, EPHA5-rs7349683, EPHA6-rs301927, LIMK2-rs5749248, and XKR4-rs4737264) were analyzed based on the results of a previous genome-wide association study. Per-allele SNP associations were assessed by a Cox regression to model the cumulative dose of nab-PTX up to the onset of severe or worsening sensory neuropathy. A total of 141 patients were enrolled in the parent study; 91(65%) were included in this sub-study. Worsening of CIPN was significantly greater in the cases with XKR4 AC compared to those with a homozygote AA (HR 1.86, 95%CI: 1.00001−3.46, p=0.049). There was no significant correlation of CIPN with any other SNP. A multivariate analysis showed that the cumulative dose of nab-PTX was most strongly correlated with CIPN (p<0.01)