Evidence against the Detectability of a Hippocampal Place Code Using Functional Magnetic Resonance Imaging

Individual hippocampal neurons selectively increase their firing rates in specific spatial locations. As a population, these neurons provide a decodable representation of space that is robust against changes to sensory- and path-related cues. This neural code is sparse and distributed, theoretically rendering it undetectable with population recording methods such as functional magnetic resonance imaging (fMRI). Existing studies nonetheless report decoding spatial codes in the human hippocampus using such techniques. Here we present results from a virtual navigation experiment in humans in which we eliminated visual- and path-related confounds and statistical limitations present in existing studies, ensuring that any positive decoding results would represent a voxel-place code. Consistent with theoretical arguments derived from electrophysiological data and contrary to existing fMRI studies, our results show that although participants were fully oriented during the navigation task, there was no statistical evidence for a place code

Assessing a Hydrodynamic Description for Instabilities in Highly Dissipative, Freely Cooling Granular Gases

An intriguing phenomenon displayed by granular flows and predicted by kinetic-theory-based models is the instability known as particle "clustering," which refers to the tendency of dissipative grains to form transient, loose regions of relatively high concentration. In this work, we assess a modified-Sonine approximation recently proposed [Garz\'o et al., Physica A 376, 94 (2007)] for a granular gas via an examination of system stability. In particular, we determine the critical length scale associated with the onset of two types of instabilities -vortices and clusters- via stability analyses of the Navier-Stokes-order hydrodynamic equations by using the expressions of the transport coefficients obtained from both the standard and the modified-Sonine approximations. We examine the impact of both Sonine approximations over a range of solids fraction \phi <0.2 for small restitution coefficients e=0.25--0.4, where the standard and modified theories exhibit discrepancies. The theoretical predictions for the critical length scales are compared to molecular dynamics (MD) simulations, of which a small percentage were not considered due to inelastic collapse. Results show excellent quantitative agreement between MD and the modified-Sonine theory, while the standard theory loses accuracy for this highly dissipative parameter space. The modified theory also remedies a (highdissipation) qualitative mismatch between the standard theory and MD for the instability that forms more readily. Furthermore, the evolution of cluster size is briefly examined via MD, indicating that domain-size clusters may remain stable or halve in size, depending on system parameters.Comment: 4 figures; to be published in Phys. Rev.

The Radio Recovery of SN 1970G: The Continuing Radio Evolution of SN 1970G

Using the Very Large Array, we have detected radio emission from the site of SN 1970G in the Sc galaxy M101. These observations are 31 years after the supernova event, making SN 1970G the longest monitored radio supernova. With flux densities of 0.12 +/- 0.020 mJy at 6 cm and 0.16 +/- 0.015 mJy at 20 cm, the spectral index of -0.24 +/- 0.20 appears to have flattened somewhat when compared with the previously reported value of -0.56 +/- 0.11, taken in 1990. The radio emission at 20 cm has decayed since the 1990 observations with a power-law index of beta_20cm = -0.28 +/- 0.13. We discuss the radio properties of this source and compare them to those of other Type II radio supernovae.Comment: 11 pages, 1 table and 2 figures; To appear in Astrophysical Journal Letter

Preparing pre-service teachers for classroom practice in a virtual world: A pilot study using Second Life

Many pre-service teachers feel under-prepared to teach students with a diverse range of needs and abilities and continue to be concerned about classroom behaviour management when undertaking practicum experiences. In order to address these concerns, teacher educators have explored alternative pedagogical approaches, including computer based simulations and immersion in virtual worlds. This paper reports on the results of a pilot study conducted with eight pre-service teachers who operated avatars in a virtual classroom created within Second Life (SL)&trade;. The pre-service teachers were able to role-play students with a diverse range of behaviours and engage in reflective discussion about their experiences. The results showed that the pre-service teachers appreciated the opportunity to engage in an authentic classroom experience without impacting on &quot;real&quot; students, but that the platform of SL proved limiting in enacting certain aspects of desired teaching pedagogy. The findings of this pilot study are discussed in relation to improving the preparation of pre-service teachers for practicum

Folding-competent and folding-defective forms of Ricin A chain have different fates following retrotranslocation from the endoplasmic reticulum

We report that a toxic polypeptide retaining the potential to refold upon dislocation from the endoplasmic reticulum (ER) to the cytosol (ricin A chain; RTA) and a misfolded version that cannot (termed RTAΔ), follow ER-associated degradation (ERAD) pathways in Saccharomyces cerevisiae that substantially diverge in the cytosol. Both polypeptides are dislocated in a step mediated by the transmembrane Hrd1p ubiquitin ligase complex and subsequently degraded. Canonical polyubiquitylation is not a prerequisite for this interaction because a catalytically inactive Hrd1p E3 ubiquitin ligase retains the ability to retrotranslocate RTA, and variants lacking one or both endogenous lysyl residues also require the Hrd1p complex. In the case of native RTA, we established that dislocation also depends on other components of the classical ERAD-L pathway as well as an ongoing ER–Golgi transport. However, the dislocation pathways deviate strikingly upon entry into the cytosol. Here, the CDC48 complex is required only for RTAΔ, although the involvement of individual ATPases (Rpt proteins) in the 19S regulatory particle (RP) of the proteasome, and the 20S catalytic chamber itself, is very different for the two RTA variants. We conclude that cytosolic ERAD components, particularly the proteasome RP, can discriminate between structural features of the same substrate

HST/STIS Spectroscopy of the Lyman-Alpha Emission Line in the Central Dominant Galaxies in A426, A1795, and A2597: Constraints on Clouds in the Intracluster Medium

We report on HST/STIS spectra of the Lyman-alpha emission in the central dominant galaxies in three rich clusters of galaxies. We find evidence for a population of clouds in the intracluster medium.We detect 10 Ly-alpha absorption systems towards the nucleus of NGC1275 with columns of N(HI) 1E12-1E14 cm-2. The detected absorption features are most consistent with associated nuclear absorption systems. There is very little nuclear absorption at the systemic velocity in NGC1275. This implies that the large columns detected in the 21 cm line towards the parsec scale radio source avoid the line of sight to the nucleus. This gas may be located in a circumnuclear disk or torus. We detect at least one and possibly two absorption features towards the extended Ly-alpha in A426. We do not detect absorption towards the extended Ly-alpha emission in A1795, and A2597 with upper limits N(HI) 1E13 cm-2 for optically thin absorbers. Our data constrain the covering factor of any high column density gas in the ICM to be less than 25%. Our results suggest that the lack of observed intermediate temperature gas is not explained by obscuration. In addition, the low columns of gas on the 100 kpc scales in the ICM suggests that (1) the rate at which cold gas accumulates in the ICM on these scales is very low, and (2) the dense nebulae in the central 10 kpc must have cooled or been deposited in situ.Comment: 6 figure

Variability of in vivo reference point indentation in skeletally mature inbred rats.

Bone Biology Laboratory [LINK]http://www.iupui.edu/~bonelab[/LINK]Reference point indentation (RPI) has emerged as a novel tool to measure material-level biomechanical properties in vivo. Human studies have been able to differentiate fracture versus non-fracture patients while a dog study has shown the technique can differentiate drug treatment effects. The goal of this study was to extend this technology to the in vivo measurement of rats, one of the most common animal models used to study bone, with assessment of intra- and inter-animal variability. Seventy-two skeletally mature male Sprague-Dawley rats were subjected to in vivo RPI on the region between the tibial diaphysis and proximal metaphysis. RPI data were assessed using a custom MATLAB program to determine several outcome parameters, including first cycle indentation distance (ID-1st), indentation distance increase (IDI), total indentation distance (TID), first cycle unloading slope (US-1st), and first cycle energy dissipation (ED-1st). Intra-animal variability ranged from 13-21% with US-1st and Tot Ed 1st-L being the least variable properties and IDI the most highly variable. Inter-animal variability ranged from 16% (US-1st) to 25% (ED-1st 31 and IDI). Based on these data, group size estimates would need to range from 9-18/group to achieve sufficient power for detecting a 25% difference in a two-group experiment. Repeat tests on the contralateral limb of a small cohort of animals (n=17) showed non-significant differences over 28 days ranging from -6% to -18%. These results provide important data on RPI variability (intra- and inter-animal) in rats that can be used to properly power future experiments using this technique.Funding for this study was provided by NIH (AR 62002 and DK100093) and the Indiana Clinical and Translational Science Institute fellowship program. The authors would like to thank Joey Wallace and David Burr for helpful comments on early drafts of this manuscript

Chewing gum benefits sustained attention in the absence of task degradation.

OBJECTIVES: The present study examined the effect of chewing gum on sustained attention and associated changes in subjective alertness. METHODS: In a within-participants design, 20 participants completed an extended version of the sustained attention response task (SART: Robertson et al., 1997), both with and without chewing gum. Self-rated measures of alertness, contentedness, and calmness were taken before and after the SART. RESULTS: Chewing gum was associated with improved attentional task performance. This finding was not contingent upon a general decrease in attentional performance and was apparent at all stages of the task. Subjective measures of alertness, contentedness, and calmness were higher following the chewing of gum. Changes in sustained attention co-varied with subjective alertness. DISCUSSION: The effects of chewing gum on attention and alertness are consistent with past literature and were not contingent on declines in attention. Additionally, we found evidence that gum-induced changes in self-rated alertness and attention are related. We found no support for the proposition that chewing gum can impair attention due to the division of resources

Phase 1b/2a trial of the superoxide dismutase mimetic GC4419 to reduce chemoradiotherapy-induced oral mucositis in patients with oral cavity or oropharyngeal carcinoma

PURPOSE: To assess the safety of the superoxide dismutase mimetic GC4419 in combination with radiation and concurrent cisplatin for patients with oral cavity or oropharyngeal cancer (OCC) and to assess the potential of GC4419 to reduce severe oral mucositis (OM). PATIENTS AND METHODS: Patients with locally advanced OCC treated with definitive or postoperative intensity modulated radiation therapy (IMRT) plus cisplatin received GC4419 by 60-minute intravenous infusion, ending \u3c60 minutes before IMRT, Monday through Friday for 3 to 7 weeks, in a dose and duration escalation study. Oral mucositis was assessed twice weekly during and weekly after IMRT. RESULTS: A total of 46 patients received GC4419 in 11 separate dosing and duration cohorts: dose escalation occurred in 5 cohorts receiving 15 to 112 mg/d over 3 weeks (n=20), duration escalation in 3 cohorts receiving 112 mg/d over 4 to 6 weeks (n=12), and then 3 additional cohorts receiving 30 or 90 mg/d over 6 to 7 weeks (n=14). A maximum tolerated dose was not reached. One dose-limiting toxicity (grade 3 gastroenteritis and vomiting with hyponatremia) occurred in each of 2 separate cohorts at 112 mg. Nausea/vomiting and facial paresthesia during infusion seemed to be GC4419 dose-related. Severe OM occurred through 60 Gy in 4 of 14 patients (29%) dosed for 6 to 7 weeks, with median duration of only 2.5 days. CONCLUSIONS: The safety of GC4419 concurrently with chemoradiation for OCC was acceptable. Toxicities included nausea/vomiting and paresthesia. Doses of 30 and 90 mg/d administered for 7 weeks were selected for further study. In an exploratory analysis, severe OM seemed less frequent and briefer than expected

A Phase 3 Study of Evolocumab (AMG 145) in Statin-Treated Japanese Patients at High Cardiovascular Risk

Evolocumab (AMG 145), a fully human monoclonal antibody against PCSK9, significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in phase 2 and 3 studies. This phase 3 study evaluated the efficacy and safety of evolocumab plus atorvastatin in Japanese patients with hyperlipidemia or mixed dyslipidemia and high cardiovascular risk. Patients were randomized to atorvastatin 5 or 20 mg/day for 4 weeks. Subsequently, patients underwent second randomization to evolocumab 140 mg biweekly (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM. Coprimary end points were % change from baseline in LDL-C at week 12 and mean of weeks 10 and 12. Secondary end points included change and % change in other lipids and proportion of patients reaching LDL-C <70 mg/dl. Adverse events and laboratory values were recorded. Four hundred four patients were randomized to study drug. At baseline, the mean (SD) age was 61 (10) years (placebo) and 62 (11) years (evolocumab); 39% and 40% were women; 14% and 12% had cerebrovascular or peripheral arterial disease; and 51% and 47% had diabetes. At entry, mean (SD) calculated LDL-C was 128 (23) mg/dL; after stabilization on atorvastatin 5 and 20 mg/day, baseline LDL-C levels were 118 (35) and 94 (24) mg/dL, respectively. Mean LDL-C reductions at week 12 for evolocumab versus placebo ranged from 67% to 76%. No imbalances were observed in adverse events between treatment groups. Efficacy and safety for Q2W or QM evolocumab dosing were similar. In conclusion, in high-risk Japanese patients receiving stable statin therapy, evolocumab markedly reduced LDL-C and was well tolerated