Showing papers by "Université de Sherbrooke published in 2007"

Charge-insensitive qubit design derived from the Cooper pair box

Abstract: Short dephasing times pose one of the main challenges in realizing a quantum computer. Different approaches have been devised to cure this problem for superconducting qubits, a prime example being the operation of such devices at optimal working points, so-called ``sweet spots.'' This latter approach led to significant improvement of ${T}_{2}$ times in Cooper pair box qubits [D. Vion et al., Science 296, 886 (2002)]. Here, we introduce a new type of superconducting qubit called the ``transmon.'' Unlike the charge qubit, the transmon is designed to operate in a regime of significantly increased ratio of Josephson energy and charging energy ${E}_{J}∕{E}_{C}$. The transmon benefits from the fact that its charge dispersion decreases exponentially with ${E}_{J}∕{E}_{C}$, while its loss in anharmonicity is described by a weak power law. As a result, we predict a drastic reduction in sensitivity to charge noise relative to the Cooper pair box and an increase in the qubit-photon coupling, while maintaining sufficient anharmonicity for selective qubit control. Our detailed analysis of the full system shows that this gain is not compromised by increased noise in other known channels.

CASINO V2.42: a fast and easy-to-use modeling tool for scanning electron microscopy and microanalysis users.

Abstract: Monte Carlo simulations have been widely used by microscopists for the last few decades. In the beginning it was a tedious and slow process, requiring a high level of computer skills from users and long computational times. Recent progress in the microelectronics industry now provides researchers with affordable desktop computers with clock rates greater than 3 GHz. With this type of computing power routinely available, Monte Carlo simulation is no longer an exclusive or long (overnight) process. The aim of this paper is to present a new user-friendly simulation program based on the earlier CASINO Monte Carlo program. The intent of this software is to assist scanning electron microscope users in interpretation of imaging and microanalysis and also with more advanced procedures including electron-beam lithography. This version uses a new architecture that provides results twice as quickly. This program is freely available to the scientific community and can be downloaded from the website: (www.gel.usherb.ca/casino).

Coupling superconducting qubits via a cavity bus.

Abstract: Microfabricated superconducting circuit elements can harness the power of quantum behaviour for information processing. Unlike classical information bits, quantum information bits (qubits) can form superpositions or mixture states of ON and OFF, offering a faster, natural form of parallel processing. Previously, direct qubit–qubit coupling has been achieved for up to four qubits, but now two independent groups demonstrate the next crucial step: communication and exchange of quantum information between two superconducting qubits via a quantum bus, in the form of a resonant cavity formed by a superconducting transmission line a few millimetres long. Using this microwave cavity it is possible to store, transfer and exchange quantum information between two quantum bits. It can also perform multiplexed qubit readout. This basic architecture lends itself to expansion, offering the possibility for the coherent interaction of many superconducting qubits. The cover illustrates a zig-zag-shaped resonant cavity or quantum bus linking two superconducting phase qubits. One of two papers that demonstrate the communication of individual quantum states between superconducting qubits via a quantum bus. This quantum bus is a resonant cavity formed by a superconducting transmission line of several millimetres. Quantum information, initially defined in one qubit on one end, can be stored in this quantum bus and at a later time retrieved by a second qubit at the other end. Superconducting circuits are promising candidates for constructing quantum bits (qubits) in a quantum computer; single-qubit operations are now routine1,2, and several examples3,4,5,6,7,8,9 of two-qubit interactions and gates have been demonstrated. These experiments show that two nearby qubits can be readily coupled with local interactions. Performing gate operations between an arbitrary pair of distant qubits is highly desirable for any quantum computer architecture, but has not yet been demonstrated. An efficient way to achieve this goal is to couple the qubits to a ‘quantum bus’, which distributes quantum information among the qubits. Here we show the implementation of such a quantum bus, using microwave photons confined in a transmission line cavity, to couple two superconducting qubits on opposite sides of a chip. The interaction is mediated by the exchange of virtual rather than real photons, avoiding cavity-induced loss. Using fast control of the qubits to switch the coupling effectively on and off, we demonstrate coherent transfer of quantum states between the qubits. The cavity is also used to perform multiplexed control and measurement of the qubit states. This approach can be expanded to more than two qubits, and is an attractive architecture for quantum information processing on a chip.

Quantum oscillations and the Fermi surface in an underdoped high-Tc superconductor.

Abstract: Two papers in this issue report notable contributions towards an understanding of high-temperature superconductivity, still an elusive goal after more than 20 years of intensive research. Doiron-Leyraud et al. report the observation of a Fermi surface in a high-temperature superconductor, a phenomenon regarded as the classic signature of a metal. Gomes et al. tackled the long-standing question of whether the gap in the electronic energy spectrum at temperatures above the critical temperature of a high-temperature superconductor is associated with electron pairing. They find that it is. With these two elegant experimental papers adding some solid new data to the mix, it is the turn of the theorists to work out the implications for superconductivity mechanisms. The observation of quantum oscillations in the electrical resistance of YBa2Cu3O6.5, is reported, establishing the existence of a well-defined Fermi surface in the ground state of underdoped copper oxides (once superconductivity is suppressed by a magnetic field). The low oscillation frequency reveals a Fermi surface made of small pockets, in contrast to the large cylinder characteristic of the overdoped regime. Despite twenty years of research, the phase diagram of high-transition-temperature superconductors remains enigmatic1,2. A central issue is the origin of the differences in the physical properties of these copper oxides doped to opposite sides of the superconducting region. In the overdoped regime, the material behaves as a reasonably conventional metal, with a large Fermi surface3,4. The underdoped regime, however, is highly anomalous and appears to have no coherent Fermi surface, but only disconnected ‘Fermi arcs’5,6. The fundamental question, then, is whether underdoped copper oxides have a Fermi surface, and if so, whether it is topologically different from that seen in the overdoped regime. Here we report the observation of quantum oscillations in the electrical resistance of the oxygen-ordered copper oxide YBa2Cu3O6.5, establishing the existence of a well-defined Fermi surface in the ground state of underdoped copper oxides, once superconductivity is suppressed by a magnetic field. The low oscillation frequency reveals a Fermi surface made of small pockets, in contrast to the large cylinder characteristic of the overdoped regime. Two possible interpretations are discussed: either a small pocket is part of the band structure specific to YBa2Cu3O6.5 or small pockets arise from a topological change at a critical point in the phase diagram. Our understanding of high-transition-temperature (high-Tc) superconductors will depend critically on which of these two interpretations proves to be correct.

Resolving photon number states in a superconducting circuit

Abstract: Electromagnetic signals are always composed of photons, although in the circuit domain those signals are carried as voltages and currents on wires, and the discreteness of the photon's energy is usually not evident. However, by coupling a superconducting quantum bit (qubit) to signals on a microwave transmission line, it is possible to construct an integrated circuit in which the presence or absence of even a single photon can have a dramatic effect. Such a system can be described by circuit quantum electrodynamics (QED)-the circuit equivalent of cavity QED, where photons interact with atoms or quantum dots. Previously, circuit QED devices were shown to reach the resonant strong coupling regime, where a single qubit could absorb and re-emit a single photon many times. Here we report a circuit QED experiment in the strong dispersive limit, a new regime where a single photon has a large effect on the qubit without ever being absorbed. The hallmark of this strong dispersive regime is that the qubit transition energy can be resolved into a separate spectral line for each photon number state of the microwave field. The strength of each line is a measure of the probability of finding the corresponding photon number in the cavity. This effect is used to distinguish between coherent and thermal fields, and could be used to create a photon statistics analyser. As no photons are absorbed by this process, it should be possible to generate non-classical states of light by measurement and perform qubit-photon conditional logic, the basis of a logic bus for a quantum computer.

Quantum information processing with circuit quantum electrodynamics

Abstract: We theoretically study single and two-qubit dynamics in the circuit QED architecture. We focus on the current experimental design [Wallraff et al., Nature (London) 431, 162 (2004); Schuster et al., Nature (London) 445, 515 (2007)] in which superconducting charge qubits are capacitively coupled to a single high-$Q$ superconducting coplanar resonator. In this system, logical gates are realized by driving the resonator with microwave fields. Advantages of this architecture are that it allows for multiqubit gates between non-nearest qubits and for the realization of gates in parallel, opening the possibility of fault-tolerant quantum computation with superconduting circuits. In this paper, we focus on one- and two-qubit gates that do not require moving away from the charge-degeneracy ``sweet spot.'' This is advantageous as it helps to increase the qubit dephasing time and does not require modification of the original circuit QED. However, these gates can, in some cases, be slower than those that do not use this constraint. Five types of two-qubit gates are discussed, these include gates based on virtual photons, real excitation of the resonator, and a gate based on the geometric phase. We also point out the importance of selection rules when working at the charge degeneracy point.

An Intrinsic Bond-Centered Electronic Glass with Unidirectional Domains in Underdoped Cuprates

Abstract: Removing electrons from the CuO2 plane of cuprates alters the electronic correlations sufficiently to produce high-temperature superconductivity. Associated with these changes are spectral-weight transfers from the high-energy states of the insulator to low energies. In theory, these should be detectable as an imbalance between the tunneling rate for electron injection and extraction-a tunneling asymmetry. We introduce atomic-resolution tunneling-asymmetry imaging, finding virtually identical phenomena in two lightly hole-doped cuprates: Ca(1.88)Na(0.12)CuO(2)Cl2 and Bi2Sr2Dy(0.2)Ca(0.8)Cu2O(8+delta). Intense spatial variations in tunneling asymmetry occur primarily at the planar oxygen sites; their spatial arrangement forms a Cu-O-Cu bond-centered electronic pattern without long-range order but with 4a(0)-wide unidirectional electronic domains dispersed throughout (a(0): the Cu-O-Cu distance). The emerging picture is then of a partial hole localization within an intrinsic electronic glass evolving, at higher hole densities, into complete delocalization and highest-temperature superconductivity.

Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements.

Abstract: There is considerable interest in the potential impact of several polyunsaturated fatty acids (PUFAs) in mitigating the significant morbidity and mortality caused by degenerative diseases of the cardiovascular system and brain. Despite this interest, confusion surrounds the extent of conversion in humans of the parent PUFA, linoleic acid or alpha-linolenic acid (ALA), to their respective long-chain PUFA products. As a result, there is uncertainty about the potential benefits of ALA versus eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). Some of the confusion arises because although mammals have the necessary enzymes to make the long-chain PUFA from the parent PUFA, in vivo studies in humans show that asymptotically equal to 5% of ALA is converted to EPA and <0.5% of ALA is converted to DHA. Because the capacity of this pathway is very low in healthy, nonvegetarian humans, even large amounts of dietary ALA have a negligible effect on plasma DHA, an effect paralleled in the omega6 PUFA by a negligible effect of dietary linoleic acid on plasma arachidonic acid. Despite this inefficient conversion, there are potential roles in human health for ALA and EPA that could be independent of their metabolism to DHA through the desaturation - chain elongation pathway.

The multifarious effects of dispersal and gene flow on contemporary adaptation

Abstract: Summary 1Dispersal and gene flow can have a variety of interacting effects on evolution. These effects can either promote or constrain adaptive divergence through either genetic or demographic routes. The relative importance of these effects is unknown because few attempts have been made to conceptually integrate and test them. 2We draw a broad distinction between situations with vs. without strong coevolutionary dynamics. This distinction is important because the adaptive peak for a given population is more mobile in the former than in the latter. This difference makes ongoing evolutionary potential more important in the presence of strong coevolutionary dynamics than in their absence. 3We advance a conceptual integration of the various effects of gene flow and dispersal on adaptive divergence. In line with other authors, but not necessarily for the same reasons, we suggest that an intermediate level of gene flow will allow the greatest adaptive divergence. 4When dispersal is quite low, we predict that an increase will have positive effects on adaptive divergence, owing to genetic/demographic rescue and ‘reinforcement.’ The rescue effect may be more important in small populations and in homogeneous environments. The reinforcement effect may be more common in large populations and in heterogeneous environments. 5Once a certain level of dispersal is reached, we predict that a further increase may have negative effects on adaptive divergence. These effects may arise if carrying capacity is exceeded or maladaptive genes are introduced. 6Many additional effects remain to be integrated into this framework, and doing so may yield novel insights into the factors influencing evolution on ecological time-scales.

Multimorbidity's many challenges

Abstract: Patients with multiple conditions are the rule rather than the exception in primary care.1 In a recent study of 21 family practices in the Saguenay region, Quebec, the prevalence of multimorbidity was 69% in 18-44 year olds, 93% in 45-64 year olds, and 98% in those aged over 65, and the number of chronic conditions varied from 2.8 in the youngest to 6.4 in the oldest.1 Other countries report a similar burden.2 3 The number of Americans with multimorbidity is estimated to rise from 60 million in 2000 to 81 million by 2020.4 Having multiple chronic medical conditions is associated with poor outcomes: patients have decreased quality of life,5 psychological distress,6 longer hospital stays, more postoperative complications, a higher cost of care, and higher mortality. Multimorbidity also affects processes of care and may result in complex self care needs7; challenging organisational problems (accessibility, coordination, consultation time); polypharmacy; increased use of emergency facilities; difficulty in applying guidelines; and fragmented, costly, and ineffective care. Yet most research and clinical practice is still based on a single disease paradigm which may not be appropriate for patients with complex and overlapping health problems. Classic clinical trials tend to emphasise efficacy at the expense of effectiveness. In doing so, they exclude patients with multiple conditions, thereby compromising the external validity and the relevance of the trials for this population.8 Research on multimorbidity is in its infancy.9 So far, most research has investigated the epidemiology of multimorbidity, its effect on physical functioning, and its measurement. Much less studied is the effect of multimorbidity on processes of care and what constitutes “best care” for these patients. Areas for potential investigation of multimorbidity fall primarily into three categories—defining and categorising the population; developing the tools needed to explore multimorbidity and its consequences; and using these tools to investigate promising processes of care. Who are the patients with several conditions? What is their risk profile? How do we distinguish multimorbidity from related concepts such as complexity, frailty, and polypharmacy? How do we classify multimorbidity and comorbidity in terms of conditions that need disparate versus congruent treatment strategies? For example, how does the patient with coronary disease, hypertension, and diabetes differ from the one with pulmonary disease, arthritis, and depression? In which situations is a subjective or an objective measure of multimorbidity more appropriate? Investigators have begun to look at several of these complex questions, but standards have not yet been developed.10 The results of prevalence studies reveal a complex picture of coexisting diseases. We now require a clear conceptual framework that includes consistent measures of multimorbidity and permits comparisons between studies. This will facilitate the next step—investigating improved processes of care. What are the best processes for making decisions in the context of multiple, often ill defined, problems and fragmentary evidence?11 How should we assess the shifting priorities of patients and providers, design adaptive responses to unpredictable aspects of the illnesses, and organise multiple resources to achieve specific health goals?11 What affects processes of care, and what constitutes best care? Which outcomes matter to these patients in which situations? How do we implement whatever best care turns out to be? Answers to these questions will require continual experimentation, with substantial innovation and reform in healthcare delivery and organisation. Models of collaborative, patient centered, and goal oriented care are more likely to meet the complex needs of patients with multimorbidity. Involving patients in the research process and making good use of mixed methods research designs that incorporate both patient and provider perspectives may also help answer complex clinical questions. The study of multimorbidity is particularly appropriate for the international research community for several reasons. Research is in its infancy, and appropriate collaboration may minimise redundancy and promote efficient and timely research. Different international communities have varied access to administrative data that can be used to paint broad pictures of caring for people with several conditions. The World Health Organization has given priority during the next decade to worldwide prevention and care of chronic illness.12 International collaboration specifically among primary care researchers may result in patient centered and low tech care practices that can be translated into practice in varied settings and across different healthcare systems. As a step towards facilitating this collaboration, we have started a virtual research community to discuss research questions specifically directed towards international communication on multimorbidity (www.med.usherbrooke.ca/cirmo/). The increasing number of primary care research networks in many countries also offers an ideal setting for collaboration to occur. The time has come not only to include people of all ages with multimorbidity in research efforts, but to focus on improving the care of this vulnerable and growing population.

Electron pockets in the Fermi surface of hole-doped high-Tc superconductors.

Abstract: A recent paper (Nature 447, 565—568 2007) described the electronic structure of a hole–doped high–temperature copper oxide superconductor in its normal metallic state. The Fermi surface observed in underdoped materials — made up of small pockets — was at odds with that of their overdoped counterparts, and quite unlike that of conventional metals. Now David LeBoeuf et al. use measurements of the Hall effect to show that these structures in the Fermi surface are electron pockets, not the 'hole' pockets suspected. This pocket formation could be a result of an enigmatic symmetry–breaking phase, similar to that seen in some electron-doped copper oxides. The implicated phase seems to be a generic property of the copper oxides, so may be expected to play a central role in shaping the properties of high–temperature superconductors. The observation of a negative Hall resistance in the magnetic-field-induced normal state of underdoped 'YBCO'materials, which reveals that these pockets are electron-like rather than hole-like. It is proposed that these electron pockets most probably arise from a reconstruction of the Fermi surface caused by the onset of a density-wave phase, as is thought to occur in the electron-doped copper oxides near the onset of antiferromagnetic order. High-temperature superconductivity in copper oxides occurs when the materials are chemically tuned to have a carrier concentration intermediate between their metallic state at high doping and their insulating state at zero doping. The underlying evolution of the electron system in the absence of superconductivity is still unclear, and a question of central importance is whether it involves any intermediate phase with broken symmetry1. The Fermi surface of the electronic states in the underdoped ‘YBCO’ materials YBa2Cu3Oy and YBa2Cu4O8 was recently shown to include small pockets2,3,4, in contrast with the large cylinder that characterizes the overdoped regime5, pointing to a topological change in the Fermi surface. Here we report the observation of a negative Hall resistance in the magnetic-field-induced normal state of YBa2Cu3Oy and YBa2Cu4O8, which reveals that these pockets are electron-like rather than hole-like. We propose that these electron pockets most probably arise from a reconstruction of the Fermi surface caused by the onset of a density-wave phase, as is thought to occur in the electron-doped copper oxides near the onset of antiferromagnetic order6,7. Comparison with materials of the La2CuO4 family that exhibit spin/charge density-wave order8,9,10,11 suggests that a Fermi surface reconstruction also occurs in those materials, pointing to a generic property of high-transition-temperature (Tc) superconductors.

hnRNP proteins and splicing control.

Abstract: Proteins of the heterogeneous nuclear ribonucleoparticles (hnRNP) family form a structurally diverse group of RNA binding proteins implicated in various functions in metazoans. Here we discuss recent advances supporting a role for these proteins in precursor-messenger RNA (pre-mRNA) splicing. Heterogeneous nuclear RNP proteins can repress splicing by directly antagonizing the recognition of splice sites, or can interfere with the binding of proteins bound to enhancers. Recently, hnRNP proteins have been shown to hinder communication between factors bound to different splice sites. Conversely, several reports have described a positive role for some hnRNP proteins in pre-mRNA splicing. Moreover, cooperative interactions between bound hnRNP proteins may encourage splicing between specific pairs of splice sites while simultaneously hampering other combinations. Thus, hnRNP proteins utilize a variety of strategies to control splice site selection in a manner that is important for both alternative and constitutive pre-mRNA splicing.

Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain.

Abstract: Several medical centers in the United States, Canada, and Europe have recently noted an increase in the incidence and severity of Clostridium difficile-associated disease (CDAD). In Pittsburgh, 10% of patients with CDAD diagnosed in 2000 to 2001 required an emergency colectomy.1 Enhanced severity of CDAD has also been reported in several other American states.2 The largest epidemic occurred in the province of Quebec, Canada, where, during the 2004 to 2005 winter, 30 hospitals reported rates over 15 per 10,000 patient-days, at least 5 times higher than historical rates.3–5 In Sherbrooke, Quebec, the incidence of CDAD among individuals aged 65 years or more increased 10-fold between 1991 and 2003, and a recent study showed that the excess mortality that could be attributed to nosocomial CDAD in 2003 to 2004 was 16.7%.6,7 This coincided with the emergence of a hypervirulent toxinotype III NAP1/027 strain of C. difficile, which produces levels of toxins A and B that are 16 to 23 times higher than historical strains, most of which were toxinotype 0.8 The same hypervirulent strain has also been found in the United Kingdom, the Netherlands, and Belgium.9–12 It used to be uncommon for patients with CDAD to require admission into an intensive care unit (ICU), but many hospitals in Quebec have noted a dramatic increase in the number of such cases since 2003.13 In that context, intensive care physicians have been frequently seeking a surgical opinion for the most severe cases, and many patients have undergone an emergency colectomy. Such a decision is largely empirical given the absence of evidence supporting a surgical approach. To improve the surgical decision-making process for patients critically ill with CDAD, we undertook a retrospective study of all patients with CDAD who, between January 1, 2003 and June 30, 2005, required admission into an ICU in 2 tertiary care hospitals of Quebec.

Impact of a Reduction in the Use of High-Risk Antibiotics on the Course of an Epidemic of Clostridium difficile-Associated Disease Caused by the Hypervirulent NAP1/027 Strain

Abstract: A series of measures were implemented, in a secondary/tertiary-care hospital in Quebec, to control an epidemic of nosocomial Clostridium difficile-associated disease (n-CDAD) caused by a virulent strain; these measures included the development of a nonrestrictive antimicrobial stewardship program. Interrupted time-series analysis was used to evaluate the impact of these measures on n-CDAD incidence. From 2003-2004 to 2005-2006, total and targeted antibiotic consumption, respectively, decreased by 23% and 54%, and the incidence of n-CDAD decreased by 60%. No change in n-CDAD incidence was noted after strengthening of infection control procedures (P=.63), but implementation of the antimicrobial stewardship program was followed by a marked reduction in incidence (P=.007). This suggests that nonrestrictive measures to optimize antibiotic usage can yield exceptional results when physicians are motivated and that such measures should be a mandatory component of n-CDAD control. The inefficacy of infection control measures targeting transmission through hospital personnel might be a result of their implementation late in the epidemic, when the environment was heavily contaminated with spores.

Polymer Micelles Stabilization on Demand through Reversible Photo-Cross-Linking

Abstract: The stability of polymer micelles, which affects the stability of encapsulation of guest molecules, may be a crucial condition for some controlled delivery applications. It is possible that polymer micelles are disintegrated after being administrated in the body due to an extreme dilution to below the critical micelle concentration of the polymer. If this happens, the entrapped guest such as a drug can leak out quickly, which renders any strategy for site-specific transport of the micelles useless. 1

Descending analgesia – When the spine echoes what the brain expects

Abstract: Changes in pain produced by psychological factors (e.g., placebo analgesia) are thought to result from the activity of specific cortical regions. However, subcortical nuclei, including the periaqueductal gray and the rostroventral medulla, also show selective activation when subjects expect pain relief. These brainstem regions send inhibitory projections to the spine and produce diffuse analgesic responses. Regrettably the precise contribution of spinal mechanisms in predicting the strength of placebo analgesia is unknown. Here, we show that expectations regarding pain radically change the strength of spinal nociceptive responses in humans. We found that contrary to expectations of analgesia, expectations of hyperalgesia completely blocked the analgesic effects of descending inhibition on spinal nociceptive reflexes. Somatosensory-evoked brain potentials and pain ratings further confirmed changes in spino-thalamo-cortical responses consistent with expectations and with changes in the spinal response. These findings provide direct evidence that the modulation of pain by expectations is mediated by endogenous pain modulatory systems affecting nociceptive signal processing at the earliest stage of the central nervous system. Expectation effects, therefore, depend as much about what takes place in the spine as they do about what takes place in the brain. Furthermore, complete suppression of the analgesic response normally produced by descending inhibition suggests that anti-analgesic expectations can block the efficacy of pharmacologically valid treatments which has important implications for clinical practice.

Early onset of vegetation growth vs. rapid green-up: impacts on juvenile mountain ungulates

Abstract: Seasonal patterns of climate and vegetation growth are expected to be altered by global warming. In alpine environments, the reproduction of birds and mammals is tightly linked to seasonality; therefore such alterations may have strong repercussions on recruitment. We used the normalized difference vegetation index (NDVI), a satellite-based measurement that correlates strongly with aboveground net primary productivity, to explore how annual variations in the timing of vegetation onset and in the rate of change in primary production during green-up affected juvenile growth and survival of bighorn sheep (Ovis canadensis), Alpine ibex (Capra ibex), and mountain goats (Oreamnos americanus) in four different populations in two continents. We indexed timing of onset of vegetation growth by the integrated NDVI (INDVI) in May. The rate of change in primary production during green-up (early May to early July) was estimated as (1) the maximal slope between any two successive bimonthly NDVI values during this period and (2) the slope in NDVI between early May and early July. The maximal slope in NDVI was negatively correlated with lamb growth and survival in both populations of bighorn sheep, growth of mountain goat kids, and survival of Alpine ibex kids, but not with survival of mountain goat kids. There was no effect of INDVI in May and of the slope in NDVI between early May and early July on juvenile growth and survival for any species. Although rapid changes in NDVI during the green-up period could translate into higher plant productivity, they may also lead to a shorter period of availability of high-quality forage over a large spatial scale, decreasing the opportunity for mountain ungulates to exploit high-quality forage. Our results suggest that attempts to forecast how warmer winters and springs will affect animal population dynamics and life histories in alpine environments should consider factors influencing the rate of changes in primary production during green-up and the timing of vegetation onset.

p21 transcription is regulated by differential localization of histone H2A.Z.

Abstract: Eukaryotic DNA is condensed many fold (e.g., 10,000) into chromatin, the basic unit of which contains 146 base pairs (bp) of DNA and an octamer of histone proteins (H2A, H2B, H3, and H4). Due to the high level of compaction, chromatin typically represses certain cellular DNA transactions, including transcription. For successful transcription, it is argued that nucleosomes need to be remodeled or evicted from promoter regions for the transcriptional machinery to be efficiently recruited to a target gene. The incorporation of histone variants into specific nucleosomes within a promoter region constitutes a mechanism by which promoter region chromatin can become more permissive to transcription initiation and elongation following receipt of a proper physiological cue. One such histone variant is H2A.Z. In Saccharomyces cerevisiae, it can elicit positive effects on gene expression (Santisteban et al. 2000; Adam et al. 2001; Larochelle and Gaudreau 2003). In addition, H2A.Z regulates genes that are proximal to telomeres and acts as a “buffer” to antagonize the spread of heterochromatin into euchromatic regions (Meneghini et al. 2003). Furthermore, recent reports from our laboratory and others (Guillemette et al. 2005; Li et al. 2005; Raisner et al. 2005; Zhang et al. 2005) have shown that H2A.Z is preferentially localized within a few nucleosomes of the initiator regions of multiple promoters in the yeast genome. Interestingly, these H2A.Z-rich loci are largely devoid of transcriptional activity, which suggests that the variant histone prepares genes for activation (Guillemette et al. 2005) and/or operates as a transcriptional repressor. Finally, yeast H2A.Z was shown to regulate nucleosome positioning, which provides mechanistic insight into how its presence can alter promoter transcriptional state (Guillemette et al. 2005). An ATP-dependent chromatin remodeling complex that specifically loads H2A.Z onto chromatin and exchanges it with H2A exists in yeast (Krogan et al. 2003; Kobor et al. 2004; Mizuguchi et al. 2004). This complex, in which the catalytic subunit is Swr1, also shares essential subunits with the NuA4 histone acetyltransferase complex (Krogan et al. 2003; Kobor et al. 2004). In addition to their importance in gene regulation, the Swr1 complex, H2A.Z, and NuA4 are all involved in the regulation of yeast chromosome stability (Krogan et al. 2004). This is noteworthy because, in mammalian cells, depletion of H2A.Z causes major nuclear and chromosomal abnormalities as witnessed by a high incidence of lagging chromosomes and chromatin bridges (Rangasamy et al. 2004). There are two homologs of Swr1 in human cells: p400/Domino (herein referred to as p400), and SRCAP (Doyon and Cote 2004; Jin et al. 2005). There are also three uncharacterized p400-type SWI2–SNF2 molecules, including hIno80 (Bakshi et al. 2006). Members of this family of SWI2/SNF2 chromatin remodeling enzymes each contain a spacer region inserted into the SWI2/SNF2 homology region (Smith and Peterson 2005). p400 was originally isolated as an E1A-associated protein (Fuchs et al. 2001), and it was also shown to interact with p53, Myc, and SV40 large T antigen (Chan et al. 2005). It is also required for E1A to induce p53-mediated apoptosis (Samuelson et al. 2005). SRCAP has been isolated as a CREB-binding protein (Johnston et al. 1999). While one report shows that both p400 and SRCAP constitute part of the same complex (Doyon et al. 2004), a recent study shows that SRCAP and p400 exist in distinct complexes with H2A.Z (Cai et al. 2005; Ruhl et al. 2006). Recently an SRCAP-containing complex was purified, and it was shown to have the ability to exchange H2A–H2B for H2A.Z–H2B in reconstituted mononucleosomes (Ruhl et al. 2006). It remains to be determined whether mammalian homolog(s) of Swr1, such as p400 and SRCAP, also catalyze H2A.Z deposition in vivo. Depletion of p400 elevates p21 synthesis to initiate premature senescence in primary human fibroblasts (Chan et al. 2005). Senescence was first observed in tissue culture cells as a stable form of cell growth arrest provoked by diverse stresses (Hayflick and Moorhead 1961; Sharpless and DePinho 2005). Recently, oncogene-induced senescence was shown to occur in various precancerous lesions both in humans and mice (Braig et al. 2005; Chen et al. 2005; Collado et al. 2005; Michaloglou et al. 2005), further suggesting that senescence acts as a defense mechanism against malignant cell development (Sager 1991; Hanahan and Weinberg 2000). Importantly, the action of p400 at p21 depends on the function of p53, a key regulator of p21 transcription (el-Deiry et al. 1993). Given the possibility of a link between p400 and H2A.Z, we questioned whether H2A.Z is also an important regulator of p21 expression. The results of this effort show that H2A.Z depletion induces p21 expression in a p53-dependent fashion, as well as the premature senescence of primary diploid fibroblasts. Similar to senescence induced by p400 depletion, inactivating p53 or p21 blocked the emergence of certain senescent phenotypes following H2A.Z depletion. In a normal setting, H2A.Z is highly enriched at discrete p53-binding sites that lie within the p21 promoter. This distinctive localization pattern depends on the presence of p53, and was detected at other p53 target gene promoters as well. The presence of p400 is required to localize H2A.Z at those loci, and purified recombinant p400 from insect cells can carry out in vitro exchange of H2A.Z–H2B dimers into chromatin. H2A.Z and p400 localization at the p53-binding sites in p21 was severely diminished following p21 induction, and this process was not dependent on active p21 transcription per se. After H2A.Z and p400 eviction from the p53-binding sites in p21, we observed that the Tip60 histone acetyltransferase had been recruited to the distal p53-binding site in the promoter to positively regulate p21 expression. Finally, overexpression of Myc, a known suppressor of p21 synthesis, significantly increased H2A.Z localization at the Myc-binding site in the TATA initiator region of the p21 promoter. This observation is consistent with the view that Myc represses p21 expression by preferentially recruiting H2A.Z-containing nucleosome(s) to this element.

Operational Definitions of Attributes of Primary Health Care: Consensus Among Canadian Experts

Abstract: PURPOSE In 2004, we undertook a consultation with Canadian primary health care experts to define the attributes that should be evaluated in predominant and proposed models of primary health care in the Canadian context. METHOD Twenty persons considered to be experts in primary health care or recommended by at least 2 peers responded to an electronic Delphi process. The expert group was balanced between clinicians (principally family physicians and nurses), academics, and decision makers from all regions in Canada. In 4 iterative rounds, participants were asked to propose and modify operational definitions. Each round incorporated the feedback from the previous round until consensus was achieved on most attributes, with a final consensus process in a face-to-face meeting with some of the experts. RESULTS Operational definitions were developed and are proposed for 25 attributes; only 5 rate as specific to primary care. Consensus on some was achieved early (relational continuity, coordination-continuity, family-centeredness, advocacy, cultural sensitivity, clinical information management, and quality improvement process). The definitions of other attributes were refined over time to increase their precision and reduce overlap between concepts (accessibility, quality of care, interpersonal communication, community orientation, comprehensiveness, multidisciplinary team, responsiveness, integration). CONCLUSION This description of primary care attributes in measurable terms provides an evaluation lexicon to assess initiatives to renew primary health care and serves as a guide for instrument selection.

The small RNA RyhB activates the translation of shiA mRNA encoding a permease of shikimate, a compound involved in siderophore synthesis.

Abstract: RyhB is a small RNA (sRNA) that downregulates about 20 genes involved in iron metabolism. It is expressed under low iron conditions and pairs with specific mRNAs to trigger their rapid degradation by the RNA degradosome. In contrast to this, another study has suggested that RyhB also activates several genes by increasing their mRNA level. Among these activated genes is shiA, which encodes a permease of shikimate, an aromatic compound participating in the biosynthesis of siderophores. Here, we demonstrate in vivo and in vitro that RyhB directly pairs at the 5'-untranslated region (5'-UTR) of the shiA mRNA to disrupt an intrinsic inhibitory structure that sequesters the ribosome-binding site (Shine-Dalgarno) and the first translation codon. This is the first demonstration of direct gene activation by RyhB, which has been exclusively described in degradation of mRNAs. Our physiological results indicate that the transported compound of the ShiA permease, shikimate, is important under conditions of RyhB expression, that is, iron starvation. This is demonstrated by growth assays in which shikimate or the siderophore enterochelin correct the growth defect observed for a ryhB mutant in iron-limited media.

Bacterial c-di-GMP Is an Immunostimulatory Molecule

Abstract: Cyclic diguanylate (c-di-GMP) is a bacterial intracellular signaling molecule. We have shown that treatment with exogenous c-di-GMP inhibits Staphylococcus aureus infection in a mouse model. We now report that c-di-GMP is an immodulator and immunostimulatory molecule. Intramammary treatment of mice with c-di-GMP 12 and 6 h before S. aureus challenge gave a protective effect and a 10,000-fold reduction in CFUs in tissues ( p S. aureus clumping factor A (ClfA) Ag produced serum with significantly higher anti-ClfA IgG Ab titers ( p