Control of Four-Level Quantum Coherence via Discrete Spectral Shaping of an Optical Frequency Comb

We present an experiment demonstrating high-resolution coherent control of a four-level atomic system in a closed (diamond) type configuration. A femtosecond frequency comb is used to establish phase coherence between a pair of two-photon transitions in cold Rb atoms. By controlling the spectral phase of the frequency comb we demonstrate the optical phase sensitive response of the diamond system. The high-resolution state selectivity of the comb is used to demonstrate the importance of the signs of dipole moment matrix elements in this type of closed-loop excitation. Finally, the pulse shape is optimized resulting in a 256% increase in the two-photon transition rate by forcing constructive interference between the mode pairs detuned from an intermediate resonance.Comment: 5 pages, 4 figures Submitted to Physical Review Letter

Direct frequency comb measurements of absolute optical frequencies and population transfer dynamics

A phase-stabilized femtosecond laser comb is directly used for high-resolution spectroscopy and absolute optical frequency measurements of one- and two-photon transitions in laser-cooled \rb atoms. Absolute atomic transition frequencies, such as the 5S$_{1/2}$ F=2 \ra 7S$_{1/2}$ F"=2 two-photon resonance measured at 788 794 768 921(44) kHz, are determined without \textit{a priori} knowledge about their values. Detailed dynamics of population transfer driven by a sequence of pulses are uncovered and taken into account for the measurement of the 5P states via resonantly enhanced two-photon transitions.Comment: 5 pages, 4 figures, submitte

High resolution atomic coherent control via spectral phase manipulation of an optical frequency comb

Sem informaçãoWe demonstrate high resolution coherent control of cold atomic rubidium utilizing spectral phase manipulation of a femtosecond optical frequency comb. Transient coherent accumulation is directly manifested by the enhancement of signal amplitude and spectral resolution via the pulse number. The combination of frequency comb technology and spectral phase manipulation enables coherent control techniques to enter a new regime with natural linewidth resolution. © 2006 The American Physical Society.We demonstrate high resolution coherent control of cold atomic rubidium utilizing spectral phase manipulation of a femtosecond optical frequency comb. Transient coherent accumulation is directly manifested by the enhancement of signal amplitude and spectral resolution via the pulse number. The combination of frequency comb technology and spectral phase manipulation enables coherent control techniques to enter a new regime with natural linewidth resolution.We demonstrate high resolution coherent control of cold atomic rubidium utilizing spectral phase manipulation of a femtosecond optical frequency comb. Transient coherent accumulation is directly manifested by the enhancement of signal amplitude and spectral resolution via the pulse number. The combination of frequency comb technology and spectral phase manipulation enables coherent control techniques to enter a new regime with natural linewidth resolution.961514Sem informaçãoSem informaçãoSem informaçãoUdem, Th., Holzwarth, R., Hänsch, T.W., (2002) Nature (London), 416, p. 233. , NATUAS. 0028-0836. 10.1038/416233aCundiff, S.T., Ye, J., (2003) Rev. Mod. Phys., 75, p. 325. , RMPHAT 0034-6861 10.1103/RevModPhys.75.325Marian, A., (2004) Science, 306, p. 2063. , SCIEAS 0036-8075 10.1126/science.1105660Marian, A., (2005) Phys. Rev. Lett., 95, p. 023001. , PRLTAO 0031-9007 10.1103/PhysRevLett.95.023001Diddams, S.A., (2001) Science, 293, p. 825. , SCIEAS 0036-8075 10.1126/science.1061171Ye, J., Ma, L.-S., Hall, J.L., (2001) Phys. Rev. Lett., 87, p. 270801. , PRLTAO 0031-9007 10.1103/PhysRevLett.87.270801Holman, K.W., (2005) Opt. Lett., 30, p. 1225. , OPLEDP 0146-9592 10.1364/OL.30.001225Jones, R.J., (2005) Phys. Rev. Lett., 94, p. 193201. , PRLTAO 0031-9007 10.1103/PhysRevLett.94.193201Gohle, C., (2005) Nature (London), 436, p. 234. , NATUAS 0028-0836 10.1038/nature03851Kuklinski, J.R., (1989) Phys. Rev. A, 40, p. 6741. , PLRAAN 1050-2947 10.1103/PhysRevA.40.6741Broers, B., Van Linden Van Den Heuvell, H.B., Noordam, L.D., (1992) Phys. Rev. Lett., 69, p. 2062. , PRLTAO 0031-9007 10.1103/PhysRevLett.69.2062Meshulach, D., Silberberg, Y., (1998) Nature (London), 396, p. 239. , NATUAS 0028-0836 10.1038/24329Balling, P., Maas, D.J., Noordam, L.D., (1994) Phys. Rev. A, 50, p. 4276. , PLRAAN 1050-2947 10.1103/PhysRevA.50.4276Chatel, B., (2003) Phys. Rev. A, 68, p. 041402. , PLRAAN 1050-2947 10.1103/PhysRevA.68.041402Oron, D., (2002) Phys. Rev. Lett., 88, p. 063004. , PRLTAO 0031-9007 10.1103/PhysRevLett.88.063004Salzmann, W., (2006) Phys. Rev. A, 73, p. 023414. , PLRAAN 1050-2947 10.1103/PhysRevA.73.023414Felinto, D., Acioli, L.H., Vianna, S.S., (2004) Phys. Rev. A, 70, p. 043403. , PLRAAN 1050-2947 10.1103/PhysRevA.70.043403Martinez, O.E., (1987) IEEE J. Quantum Electron., 23, p. 59. , IEJQA7 0018-9197 10.1109/JQE.1987.1073201Yoon, T.H., (2001) Phys. Rev. A, 63, p. 011402. , PLRAAN 1050-2947 10.1103/PhysRevA.63.011402Vala, J., (2001) Phys. Rev. A, 63, p. 013412. , PLRAAN 1050-2947 10.1103/PhysRevA.63.013412We thank funding support from ONR, NSF, and NIST

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

Valaciclovir to prevent Cytomegalovirus mediated adverse modulation of the immune system in ANCA-associated vasculitis (CANVAS):study protocol for a randomised controlled trial

BACKGROUND: The ANCA-associated vasculitides (AAV) are systemic autoimmune inflammatory disorders characterised by necrotising inflammation affecting small to medium-sized blood vessels. Despite improvements in survival, infection and cardiovascular disease remain leading causes of morbidity and mortality. Considerable evidence suggests that CD4 + CD28null T-cell expansions, predominantly seen in Cytomegalovirus (CMV) seropositive individuals, are associated with systemic dysregulation of immune function leading to a heightened risk of infection and cardiovascular disease. In patients with AAV, CD4 + CD28null expansions are driven by CMV and are associated with an increased risk of infection and mortality. The aim of this study is to explore in detail the ways in which CMV modulates the immune system and to determine whether treatment with valaciclovir blocks subclinical CMV reactivation in CMV seropositive AAV patients and ameliorates the CMV-induced adverse effects on the immune system. METHODS/DESIGN: CANVAS is a single-centre prospective open-label randomised controlled proof-of-concept trial of 50 adult CMV seropositive patients with stable AAV. Participants will be randomly allocated to receive valaciclovir orally (2 g QDS or reduced according to renal function) or no additional treatment for 6 months with an additional 6-month follow-up period. The primary outcome is the proportion of patients with CMV reactivation, as assessed by measurable viral load on quantitative blood and urine CMV polymerase chain reaction. The secondary outcomes are safety, change in the proportion of CD4+ CMV-specific T-cell population (defined as CD4 + CD28null cells) and change in soluble markers of inflammation from baseline to 6 months. Further tertiary and exploratory outcomes include persistence of the effect of valaciclovir on the proportion of CD4 + CD28null cells at 6 months post completion of treatment, change in the immune phenotype of CD4+ T cells and change in blood pressure and arterial stiffness parameters from baseline to 6 months. DISCUSSION: The results of this study will enable larger studies to be conducted to determine whether by controlling subclinical CMV reactivation, we can improve clinical endpoints such as infection and cardiovascular disease. The potential impact of this study is not limited to AAV, as CD4 + CD28null cells have been linked to adverse outcomes in other inflammatory conditions and in the context of an ageing immune system. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01633476 (registered 29 June 2012). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-016-1482-2) contains supplementary material, which is available to authorized users

Innate Immune Responses of Drosophila melanogaster Are Altered by Spaceflight

Alterations and impairment of immune responses in humans present a health risk for space exploration missions. The molecular mechanisms underpinning innate immune defense can be confounded by the complexity of the acquired immune system of humans. Drosophila (fruit fly) innate immunity is simpler, and shares many similarities with human innate immunity at the level of molecular and genetic pathways. The goals of this study were to elucidate fundamental immune processes in Drosophila affected by spaceflight and to measure host-pathogen responses post-flight. Five containers, each containing ten female and five male fruit flies, were housed and bred on the space shuttle (average orbit altitude of 330.35 km) for 12 days and 18.5 hours. A new generation of flies was reared in microgravity. In larvae, the immune system was examined by analyzing plasmatocyte number and activity in culture. In adults, the induced immune responses were analyzed by bacterial clearance and quantitative real-time polymerase chain reaction (qPCR) of selected genes following infection with E. coli. The RNA levels of relevant immune pathway genes were determined in both larvae and adults by microarray analysis. The ability of larval plasmatocytes to phagocytose E. coli in culture was attenuated following spaceflight, and in parallel, the expression of genes involved in cell maturation was downregulated. In addition, the level of constitutive expression of pattern recognition receptors and opsonins that specifically recognize bacteria, and of lysozymes, antimicrobial peptide (AMP) pathway and immune stress genes, hallmarks of humoral immunity, were also reduced in larvae. In adults, the efficiency of bacterial clearance measured in vivo following a systemic infection with E. coli post-flight, remained robust. We show that spaceflight altered both cellular and humoral immune responses in Drosophila and that the disruption occurs at multiple interacting pathways

Harnessing hypoxic adaptation to prevent, treat, and repair stroke

The brain demands oxygen and glucose to fulfill its roles as the master regulator of body functions as diverse as bladder control and creative thinking. Chemical and electrical transmission in the nervous system is rapidly disrupted in stroke as a result of hypoxia and hypoglycemia. Despite being highly evolved in its architecture, the human brain appears to utilize phylogenetically conserved homeostatic strategies to combat hypoxia and ischemia. Specifically, several converging lines of inquiry have demonstrated that the transcription factor hypoxia-inducible factor-1 (HIF1-1) mediates the activation of a large cassette of genes involved in adaptation to hypoxia in surviving neurons after stroke. Accordingly, pharmacological or molecular approaches that engage hypoxic adaptation at the point of one of its sensors (e.g., inhibition of HIF prolyl 4 hydroxylases) leads to profound sparing of brain tissue and enhanced recovery of function. In this review, we discuss the potential mechanisms that could subserve protective and restorative effects of augmenting hypoxic adaptation in the brain. The strategy appears to involve HIF-dependent and HIF-independent pathways and more than 70 genes and proteins activated transcriptionally and post-transcriptionally that can act at cellular, local, and system levels to compensate for oxygen insufficiency. The breadth and depth of this homeostatic program offers a hopeful alternative to the current pessimism towards stroke therapeutics

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Acute Versus Chronic Loss of Mammalian Azi1/Cep131 Results in Distinct Ciliary Phenotypes

Defects in cilium and centrosome function result in a spectrum of clinically-related disorders, known as ciliopathies. However, the complex molecular composition of these structures confounds functional dissection of what any individual gene product is doing under normal and disease conditions. As part of an siRNA screen for genes involved in mammalian ciliogenesis, we and others have identified the conserved centrosomal protein Azi1/Cep131 as required for cilia formation, supporting previous Danio rerio and Drosophila melanogaster mutant studies. Acute loss of Azi1 by knock-down in mouse fibroblasts leads to a robust reduction in ciliogenesis, which we rescue by expressing siRNA-resistant Azi1-GFP. Localisation studies show Azi1 localises to centriolar satellites, and traffics along microtubules becoming enriched around the basal body. Azi1 also localises to the transition zone, a structure important for regulating traffic into the ciliary compartment. To study the requirement of Azi1 during development and tissue homeostasis, Azi1 null mice were generated (Azi1(Gt/Gt)). Surprisingly, Azi1(Gt/Gt) MEFs have no discernible ciliary phenotype and moreover are resistant to Azi1 siRNA knock-down, demonstrating that a compensation mechanism exists to allow ciliogenesis to proceed despite the lack of Azi1. Cilia throughout Azi1 null mice are functionally normal, as embryonic patterning and adult homeostasis are grossly unaffected. However, in the highly specialised sperm flagella, the loss of Azi1 is not compensated, leading to striking microtubule-based trafficking defects in both the manchette and the flagella, resulting in male infertility. Our analysis of Azi1 knock-down (acute loss) versus gene deletion (chronic loss) suggests that Azi1 plays a conserved, but non-essential trafficking role in ciliogenesis. Importantly, our in vivo analysis reveals Azi1 mediates novel trafficking functions necessary for flagellogenesis. Our study highlights the importance of both acute removal of a protein, in addition to mouse knock-out studies, when functionally characterising candidates for human disease

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)