Large-Area Atom Interferometry with Frequency-Swept Raman Adiabatic Passage

We demonstrate light-pulse atom interferometry with large-momentum-transfer atom optics based on stimulated Raman transitions and frequency-swept adiabatic rapid passage. Our atom optics have produced momentum splittings of up to 30 photon recoil momenta in an acceleration-sensitive interferometer for laser cooled atoms. We experimentally verify the enhancement of phase shift per unit acceleration and characterize interferometer contrast loss. By forgoing evaporative cooling and velocity selection, this method lowers the atom shot-noise-limited measurement uncertainty and enables large-area atom interferometry at higher data rates.Charles Stark Draper Laboratory (Fellowship

The Effect of Type II Diabetes Mellitus on Oxygen Uptake Kinetics during Heavy Exercise

The kinetics of oxygen uptake (Vo2) during the rest to exercise transition are thought to be modulated by intracellular metabolic processes. Diabetes has been shown to slow Vo2 kinetics, likely due to the impact of diabetes upon microvascular oxygen exchange (Padilla et al, 2007). However, to date, recovery from exercise has yet to be studied in these patients. Thus, the purpose of this study was to test the hypothesis that the existence of diabetes would hamper Vo2 kinetics during transitions to and from heavy leg cycling (H: Supra-LT). Nine subjects (4 control, 5 diabetic) completed three separate H exercise bouts. Vo2 was measured continuously at the mouth during exercise and recovery for each bout. During the on-transient, the total amplitude was decreased (Atot: Control 2.16±0.29 vs Diabetic 1.33±0.42 L/min, p=0.01). In an attempt to correct for differences in Atot, the rate of change in Vo2 (A1/T1 ) was calculated. This variable was significant reduced in diabetics during both the on-(A1/T1: Control 0.059±0.03 vs Diabetic 0.016±0.01, p=0.02), and off-transients (Control -0.10±0.10 vs Diabetic 0.035±0.012, p=0.09). In addition, the time constant during the on-transition was greatly slowed in diabetes (Tau: Control 24.07±8.39 vs Diabetic 76.76±37.94 sec, p=0.03). These findings suggest strongly that diabetes and it’s sequelae lead to impairments in oxidative metabolism during both exercise and recovery, which would serve to cause a faster rate of fatigue and a longer temporal course of recovery

Robust Ramsey sequences with Raman adiabatic rapid passage

We present a method for robust timekeeping in which alkali-metal atoms are interrogated in a Ramsey sequence based on stimulated Raman transitions with optical photons. To suppress systematic effects introduced by differential ac Stark shifts and optical intensity gradients, we employ atom optics derived from Raman adiabatic rapid passage (ARP). Raman ARP drives coherent transfer between the alkali-metal hyperfine ground states via a sweep of the Raman detuning through the two-photon resonance. Our experimental implementation of Raman ARP reduced the phase sensitivity of Ramsey sequences to Stark shifts in [superscript 133]Cs atoms by about two orders of magnitude, relative to fixed-frequency Raman transitions. This technique also preserved Ramsey fringe contrast for cloud displacements reaching the 1/e[superscript 2] intensity radius of the laser beam. In a magnetically unshielded apparatus, second-order Zeeman shifts limited the fractional frequency uncertainty to ~3.5 × 10[superscript −12] after about 2500 s of averaging.Charles Stark Draper Laboratory (Fellowship Program)Charles Stark Draper Laborator

Carotid Baroreflex Control of Heart Rate is Enhanced during Whole-body Heat Stress

Whole-body heat stress (WBH) reduces orthostatic tolerance. While impaired carotid baroreflex (CBR) function during WBH has been reported, study design considerations may limit interpretation of previous findings. We sought to test the hypothesis that CBR function is unaltered during WBH. CBR function was assessed in ten subjects using 5-sec trials of neck pressure (45, 30 and 15 Torr) and neck suction (-20, -40, -60 and - 80 Torr) during normothermia (NT) and passive WBH (Δ core temp ~1 °C). Analysis of stimulus response curves (4-parameter logistic model) for CBR control of heart rate (CBR-HR) and mean arterial pressure (CBR-MAP), as well as separate 2-way ANOVA of the hypo- and hypertensive stimuli (factor 1: thermal condition, factor 2: chamber pressure) were performed. For CBR-HR, maximal gain was increased during WBH (-0.73±0.37) compared to NT (-0.39±0.11, p=0.03). In addition, the CBR-HR responding range was increased during WBH (32±15) compared to NT (18±8 bpm, p=0.03). Separate analysis of hypertensive stimulation revealed enhanced HR responses during WBH at -40, -60 and -80 Torr (condition*chamber pressure interaction, p=0.049) compared to NT. For CBR-MAP, both logistic analysis and separate 2-way ANOVA revealed no differences during WBH. Therefore, despite marked orthostatic intolerance observed during WBH, CBR control of heart rate (enhanced) and arterial pressure (no change) is well-preserved

The Impact of Physiologic Reductions In Blood Pressure Upon Oxygen Uptake During Moderate Intensity Leg Cycling

INTRODUCTION: Control of oxygen uptake (VO2) during the rest-to-exercise transition is thought to be dominated by intracellular processes rather than oxygen delivery. However, large changes in arterial pressure (i.e., supraphysiologic) have been shown to alter VO2 and its kinetics. Importantly, no studies have investigated the consequence of physiologic alterations in blood pressure on VO2 and its kinetics during exercise in humans. PURPOSE: The aim of this preliminary study was to assess the effect of modest reductions in MAP achieved via neck suction upon Vo2 across the rest-exercise transition, to test the hypothesis that physiologic reductions in arterial pressure during moderate intensity, steady-state exercise will not alter VO2. METHODS: Five subjects completed four exercise trials of 6 minute leg cycling at the workloads 50% of VO2max. Each workload was completed with and without carotid baroreceptor loading (i.e., Neck Suction: blood pressure lowering stimulation) with a 20 minute resting period between trials. Heart rate, mean arterial pressure (MAP), and VO2 at the mouth, were continuously measured while upper arm blood pressure was taken every minute. RESULTS: MAP tended to be reduced during the Neck Suction condition (delta MAP: Control 13.0±8.7 vs Neck Suction 6.3±6.3 mm Hg, P=0.079). However, there was no main effect for exercise condition on VO2 (Control 13.25±1.70 vs Neck Suction 13.17±1.72 ml/kg/min, P=0.61). In addition, the on-transient mean response time was not different between groups (Control 46.7±27.2 vs Neck Suction 40.9±16.2 s). CONCLUSIONS: These preliminary findings indicate that oxygen uptake or its kinetics during moderate intensity leg cycling are not affected by modest reductions in blood pressure

Adjuvant chemotherapy with or without bevacizumab in patients with resected non-small-cell lung cancer (E1505): an open-label, multicentre, randomised, phase 3 trial.

BackgroundAdjuvant chemotherapy for resected early-stage non-small-cell lung cancer (NSCLC) provides a modest survival benefit. Bevacizumab, a monoclonal antibody directed against VEGF, improves outcomes when added to platinum-based chemotherapy in advanced-stage non-squamous NSCLC. We aimed to evaluate the addition of bevacizumab to adjuvant chemotherapy in early-stage resected NSCLC.MethodsWe did an open-label, randomised, phase 3 trial of adult patients (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status of 0 or 1 and who had completely resected stage IB (≥4 cm) to IIIA (defined by the American Joint Committee on Cancer 6th edition) NSCLC. We enrolled patients from across the US National Clinical Trials Network, including patients from the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) affiliates in Europe and from the Canadian Cancer Trials Group, within 6-12 weeks of surgery. The chemotherapy regimen for each patient was selected before randomisation and administered intravenously; it consisted of four 21-day cycles of cisplatin (75 mg/m2 on day 1 in all regimens) in combination with investigator's choice of vinorelbine (30 mg/m2 on days 1 and 8), docetaxel (75 mg/m2 on day 1), gemcitabine (1200 mg/m2 on days 1 and 8), or pemetrexed (500 mg/m2 on day 1). Patients in the bevacizumab group received bevacizumab 15 mg/kg intravenously every 21 days starting with cycle 1 of chemotherapy and continuing for 1 year. We randomly allocated patients (1:1) to group A (chemotherapy alone) or group B (chemotherapy plus bevacizumab), centrally, using permuted blocks sizes and stratified by chemotherapy regimen, stage of disease, histology, and sex. No one was masked to treatment assignment, except the Data Safety and Monitoring Committee. The primary endpoint was overall survival, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00324805.FindingsBetween June 1, 2007, and Sept 20, 2013, 1501 patients were enrolled and randomly assigned to the two treatment groups: 749 to group A (chemotherapy alone) and 752 to group B (chemotherapy plus bevacizumab). 383 (26%) of 1458 patients (with complete staging information) had stage IB, 636 (44%) had stage II, and 439 (30%) had stage IIIA disease (stage of disease data were missing for 43 patients). Squamous cell histology was reported for 422 (28%) of 1501 patients. All four cisplatin-based chemotherapy regimens were used: 377 (25%) patients received vinorelbine, 343 (23%) received docetaxel, 283 (19%) received gemcitabine, and 497 (33%) received pemetrexed. At a median follow-up of 50·3 months (IQR 32·9-68·0), the estimated median overall survival in group A has not been reached, and in group B was 85·8 months (95% CI 74·9 to not reached); hazard ratio (group B vs group A) 0·99 (95% CI 0·82-1·19; p=0·90). Grade 3-5 toxicities of note (all attributions) that were reported more frequently in group B (the bevacizumab group) than in group A (chemotherapy alone) were overall worst grade (ie, all grade 3-5 toxicities; 496 [67%] of 738 in group A vs 610 [83%] of 735 in group B), hypertension (60 [8%] vs 219 [30%]), and neutropenia (241 [33%] vs 275 [37%]). The number of deaths on treatment did not differ between the groups (15 deaths in group A vs 19 in group B). Of these deaths, three in group A and ten in group B were considered at least possibly related to treatment.InterpretationAddition of bevacizumab to adjuvant chemotherapy did not improve overall survival for patients with surgically resected early-stage NSCLC. Bevacizumab does not have a role in this setting and should not be considered as an adjuvant therapy for patients with resected early-stage NSCLC.FundingNational Cancer Institute of the National Institutes of Health

Nucleation of vortex arrays in rotating anisotropic Bose-Einstein condensates

The nucleation of vortices and the resulting structures of vortex arrays in dilute, trapped, zero-temperature Bose-Einstein condensates are investigated numerically. Vortices are generated by rotating a three-dimensional, anisotropic harmonic atom trap. The condensate ground state is obtained by propagating the Gross-Pitaevskii equation in imaginary time. Vortices first appear at a rotation frequency significantly larger than the critical frequency for vortex stabilization. This is consistent with a critical velocity mechanism for vortex nucleation. At higher frequencies, the structures of the vortex arrays are strongly influenced by trap geometry.Comment: 5 pages, two embedded figures. To appear in Phys. Rev. A (RC

Seasonal changes in patterns of gene expression in avian song control brain regions.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Photoperiod and hormonal cues drive dramatic seasonal changes in structure and function of the avian song control system. Little is known, however, about the patterns of gene expression associated with seasonal changes. Here we address this issue by altering the hormonal and photoperiodic conditions in seasonally-breeding Gambel's white-crowned sparrows and extracting RNA from the telencephalic song control nuclei HVC and RA across multiple time points that capture different stages of growth and regression. We chose HVC and RA because while both nuclei change in volume across seasons, the cellular mechanisms underlying these changes differ. We thus hypothesized that different genes would be expressed between HVC and RA. We tested this by using the extracted RNA to perform a cDNA microarray hybridization developed by the SoNG initiative. We then validated these results using qRT-PCR. We found that 363 genes varied by more than 1.5 fold (>log(2) 0.585) in expression in HVC and/or RA. Supporting our hypothesis, only 59 of these 363 genes were found to vary in both nuclei, while 132 gene expression changes were HVC specific and 172 were RA specific. We then assigned many of these genes to functional categories relevant to the different mechanisms underlying seasonal change in HVC and RA, including neurogenesis, apoptosis, cell growth, dendrite arborization and axonal growth, angiogenesis, endocrinology, growth factors, and electrophysiology. This revealed categorical differences in the kinds of genes regulated in HVC and RA. These results show that different molecular programs underlie seasonal changes in HVC and RA, and that gene expression is time specific across different reproductive conditions. Our results provide insights into the complex molecular pathways that underlie adult neural plasticity

Genome-wide analysis reveals the extent of EAV-HP integration in domestic chicken

Background: EAV-HP is an ancient retrovirus pre-dating Gallus speciation, which continues to circulate in modern chicken populations, and led to the emergence of avian leukosis virus subgroup J causing significant economic losses to the poultry industry. We mapped EAV-HP integration sites in Ethiopian village chickens, a Silkie, Taiwan Country chicken, red junglefowl Gallusgallus and several inbred experimental lines using whole-genome sequence data. Results: An average of 75.22 ± 9.52 integration sites per bird were identified, which collectively group into 279 intervals of which 5% are common to 90% of the genomes analysed and are suggestive of pre-domestication integration events. More than a third of intervals are specific to individual genomes, supporting active circulation of EAV-HP in modern chickens. Interval density is correlated with chromosome length (P<2.31−6), and 27 % of intervals are located within 5 kb of a transcript. Functional annotation clustering of genes reveals enrichment for immune-related functions (P<0.05). Conclusions: Our results illustrate a non-random distribution of EAV-HP in the genome, emphasising the importance it may have played in the adaptation of the species, and provide a platform from which to extend investigations on the co-evolutionary significance of endogenous retroviral genera with their hosts