bluuebunny/crossref_metadata_2025 huggingface dataset:
Stem cells in the mammalian eye: a tool for retinal repair
Authors: YOUNG MICHAEL J.
Published: February 2006

Degenerative diseases and traumatic injuries of the central nervous system (CNS) are major causes of long‐term disability, whether such insults impact the brain, retina, or spinal cord. Substantial tissue destruction can be sustained by these complex structures without loss of life, while the lack of effective CNS regeneration frequently results in a marked degradation in quality of life. Only recently has it become clear that an enormous potential for regeneration is present within the mammalian CNS. The challenge now presented to researchers is to harness this potential to treat disease. Recent studies showing that stem and progenitor cells can be isolated from the mammalian retina have prompted many researchers to develop strategies aimed at restoring function to the diseased retina. This review summarizes a number of issues related to this goal, including retinal development, transplantation immunology, tissue engineering, and large animal studies. The application of these divergent disciplines to stem cell technology is vital to the development of the novel strategies needed to make retinal transplantation a clinical success.
Allogeneic hematopoietic stem cell transplantation: state of the art and new perspectives
Authors: RINGDÉN OLLE , LE BLANC KATARINA
Published: February 2006

Allogeneic hematopoietic stem cell transplantation (ASCT) is a well‐established therapy for leukemias and other immunohematopoietic disorders. In more recent years, bone marrow as stem cell source has been replaced by peripheral blood stem cells, which results in faster engraftment. Cord blood grafts are increasingly used. Conditioning prior to transplant may be myeloablative or nonmyeloablative. The latter is used preferentially in patients with high age or organ impairment. Isolation in the hospital during posttransplant pancytopenia has been challenged by promising results using home care. PCR diagnosis and new antifungal and antiviral treatment have reduced morbidity and mortality. The major threat to a successful outcome after ASCT is leukemic relapse. PCR techniques to detect recipient cells in the leukemic cell lineage or minimal residual disease enable early detection of leukemic cells. Donor lymphocyte infusions have an antileukemic effect. ASCT has shown an antitumor effect in metastatic cancers from breast, kidney, colon, ovaries, prostate and pancreas. Mesenchymal stem cells may be derived from bone marrow and have the capacity to differentiate into several mesenchymal tissues, such as bone, cartilage and fat. They seem to escape the immune system and have immunomodulatory effects in vitro and in vivo. To conclude, ASCT is a potent immunotherapy.
Stem cells and diabetes treatment
Authors: MADSEN OLE DRAGSBÆK
Published: February 2006

Diabetes mellitus types 1 and 2 are characterized by absolute versus relative lack of insulin‐producing β cells, respectively. Reconstitution of a functional β‐cell mass by cell therapy – using organ donor islets of Langerhans – has been demonstrated to restore euglycaemia in the absence of insulin treatment. This remarkable achievement has stimulated the search for appropriate stem cell sources from which adequate expansion and maturation of therapeutic β cells can be achieved. This recent activity is reviewed and presented with particular focus on directed differentiation from pluripotent embryonic stem cells (versus other stem/progenitor cell sources) based on knowledge from pancreatic β‐cell development and the parallel approach to controlling endogenous β‐cell neogenesis.
Middle cerebral artery occlusion in Macaca fascicularis: acute and chronic stroke evolution
Authors: D'Arceuil Helen E. , Duggan Michael , He Julian , Pryor Johnny , de Crespigny Alex
Published: February 2006

Background 
An intravascular stroke model designed for magnetic resonance imaging was developed in Macaca fascicularis (M. fascicularis) to characterize serial stroke lesion evolution. This model produces a range of stroke lesion sizes which closely mimics human stroke evolution. This paper describes the care of animals undergoing this stroke procedure, the range of outcomes we experienced and the cause of mortality in this model.

Methods  Anesthesia was induced with atropine and ketamine and maintained with isoflurane or propofol. Non‐invasive blood pressure, oxygen saturation, heart rate, respiration rate, temperature and end tidal CO2 were monitored continuously. The stroke was created by occluding a distal branch of the middle cerebral artery. During catheter placement animals were heparinized and vasospasm was minimized using verapamil.

Results  Anesthetic induction and maintenance were smooth. Animals with small strokes showed very rapid recovery, were able to ambulate and self‐feed within 2 hours of recovery. Animals with strokes of ≥4% of the hemispheric volume required lengthy observation during recovery and parenteral nutrition. Large strokes resulted in significant brain edema, herniation and brainstem compression.

Conclusions  Intracerebral hemorrhage and or subarachnoid hemorrhage coupled with a stroke of any size was acutely fatal. In the absence of an effective acute stroke therapy, the spectrum of outcomes seen in our primate model is very similar to that observed in human stroke patients.
Molecular diversity of HLA‐A*19 group of alleles in south Indian population
Authors: Vettriselvi V. , Vijayalakshmi K. , Suganya S. , Krishnan M. , Paul S. F. D. , Jayanth V.
Published: February 2006

To determine the genetic diversity of the human leucocyte antigen (HLA)‐A*19 group of alleles in the south Indian Tamil population, we studied 100 random healthy unrelated individuals. The frequency of HLA‐A*19 was 37% with A*33 (45.9%), A*32 (29.7%), A*31 (16.2%), A*30 (5.4%), A*29 (2.7%) and A*74 (0%). The frequency distribution of the HLA‐A*19 alleles was distinct and revealed marked similarities and variations with other populations
Thyroid autoantibody production is influenced by exon 1 and promoter CTLA‐4 polymorphisms in patients with Hashimoto's thyroiditis
Authors: Zaletel K. , Krhin B. , Gaberšček S. , Hojker S.
Published: February 2006

Strong genetic susceptibility to thyroid autoantibody (TAb) diathesis has been shown and one of the major genes involved is probably CTLA‐4 gene. Our recent study of patients with Graves’ disease has demonstrated that exon 1 CTLA‐4 gene polymorphism influences higher TAb production. Here, we evaluated the influence of exon 1 and promoter CTLA‐4 polymorphisms on TAb production in 109 newly diagnosed patients with Hashimoto's thyroiditis (HT). Serum TSH, thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) were measured. 49 A/G and −318 C/T polymorphisms were detected using polymerase chain reaction amplification of genomic DNA and restriction fragment length polymorphism analysis. Patients with AG and GG genotype had significantly higher TPOAb median values compared to patients with AA genotype (P < 0.003). Similarly, TgAb median value was significantly higher in AG patients and in the entire G‐allele carrying group (P < 0.02). Compared to both T‐allele carrying genotypes, CC genotype presented with significantly higher TPOAb median value (P < 0.02), whereas TgAb median values did not differ significantly between various genotypes. In conclusion, our results indicate that G allele influences higher TPOAb and TgAb production, whereas C allele affects especially TPOAb production in patients with HT. Therefore, our findings provide further evidence that CTLA‐4 is a major TAb susceptibility gene.
Vicinal Diamino Functionalities as Privileged Structural Elements in Biologically Active Compounds and Exploitation of their Synthetic Chemistry
Authors: Saibabu Kotti S. R. S. , Timmons Cody , Li Guigen
Published: February 2006

The chemistry, synthetic routes and medicinal properties of vicinal diamines and imidazolines are discussed. Synthetic routes towards chemically and pharmaceutically important molecules containing vicinal diamine functionality are discussed in detail. This mini review article covers the new developments of diamine chemistry between 2000 and 2005.
Peptide‐based Molecules in Angiogenesis
Authors: D'Andrea Luca Domenico , Del Gatto Annarita , Pedone Carlo , Benedetti Ettore
Published: February 2006

Angiogenesis refers to the process of remodeling the vascular tissue characterized by the branching out of a new blood vessel from a pre‐existing vessel. Angiogenesis is particularly active during embryogenesis, while during adult life it is quiescent and limited to particular physiologic phenomena. Recently, the study of molecular mechanisms of angiogenesis has stirred renewed interest due to the recognition of the role played by angiogenesis in several pathologies of significant medical impact, such as cancer and cardiovascular disease, and due to the pharmacologic interest rising from the possibility of modulating these phenomena. Antibodies, peptides and small molecules targeting active endothelial cells represent an innovative tool in therapeutic and diagnostic fields. In this study, we reviewed the literature of peptide and peptidomimetics in angiogenesis and their potential applications. Two specific protein systems, namely the vascular endothelial growth factor and its receptor and integrins, will be discussed in detail.
Simulation of oil spills near environmentally sensitive areas in Egyptian coastal waters
Authors: Nasr Peter , Smith Edward
Published: February 2006

Oil spills in Egyptian coastal waters have a direct impact on the national economy because of the potential environmental damage, and the corresponding negative effect on tourism. Computer simulations of oil spills were performed for four environmentally sensitive areas along Egyptian coasts using an existing oil spill model that incorporates the important variables and processes affecting oil transport in seawater. The expected slick trajectory and variation of oil properties with time were calculated for a proposed spill scenario at each site. Water current maps, the most critical model input parameter with respect to spill trajectory, were developed for each location. The simulations demonstrated that the most important oil property affecting spill response decisions and operations is the emulsion viscosity, in that it indicates when, where, and how responders can intervene for cleanup.
Philosophy of causation: blind alleys exposed; promising directions highlighted
Authors: Hall Ned
Published: February 2006

Contemporary philosophical work on causation is a tangled mess of disparate aims, approaches, and accounts. Best to cut through it by means of ruthless but, hopefully, sensible judgments. The ones that follow are designed to sketch the most fruitful avenues for future work.
Consciousness, Theories of
Authors: Kriegel Uriah
Published: February 2006

Phenomenal consciousness is the property mental states, events, and processes have when, and only when, there is something it is like for their subject to undergo them, or be in them. What it is like to have a conscious experience is customarily referred to as the experience's phenomenal character. Theories of consciousness attempt to account for this phenomenal character. This article surveys the currently prominent theories, paying special attention to the various attempts to explain a state's phenomenal character in terms of its representational content.
Two myths about special relativity
Authors: Baierlein Ralph
Published: February 2006

Misconceptions about special relativity theory are common and pernicious. I address two such misconceptions: the low-speed behavior of the Lorentz transformation and the meaning of the phrase, “the constancy of the speed of light,” as Einstein used it in 1905.
Proportional feedback control of chaos in a simple electronic oscillator
Authors: Wiener Richard J. , Callan Kristine E. , Hall Stephen C. , Olsen Thomas
Published: February 2006

We demonstrate the control of chaos in a nonlinear circuit constructed from readily available electronic components. Control is achieved using recursive proportional feedback, which is applicable to chaotic dynamics in highly dissipative systems and can be implemented using experimental data in the absence of model equations. The application of recursive proportional feedback to a simple electronic oscillator provides an undergraduate laboratory problem for exploring proportional feedback algorithms used to control chaos.
Force-versus-time curves during collisions between two identical steel balls
Authors: Hessel R. , Perinotto A. C. , Alfaro R. A. M. , Freschi A. A.
Published: February 2006

We describe a numerical procedure for plotting the force-versus-time curves in elastic collisions between identical conducting balls. A system of parametric equations relating the force and the time to a dimensionless parameter is derived from the assumption of a force compatible with Hertz’s theory of collision. A simple experimental arrangement consisting of a mechanical system of colliding balls and an electrical circuit containing a crystal oscillator and an electronic counter is used to measure the collision time as a function of the energy of impact. From the data we can determine the relevant parameters. The calculated results agree very well with the expected values and are consistent with the assumption that the collisions are elastic.
ANALYTICAL EXPRESSIONS OF THE ORDER PARAMETERS NEAR THE TRANSITION TEMPERATURES IN THE SPIN-3/2 ISING SYSTEM WITH BILINEAR AND BIQUADRATIC INTERACTIONS
Authors: CANKO OSMAN , KESKIN MUSTAFA
Published: February 2006

Analytical expressions of the order parameters near the transition temperatures in the spin-3/2 Ising system with bilinear (J) and biquadratic (K) interactions are presented for various values of J/K. First, we obtain the free energy expression and the equations to determine order parameters by using the mean-field approximation. Then, the order parameters are expressed in the vicinity of the transition temperatures in which these expressions are very important to study the dynamics of the system by means of Onsager's theory of irreversible thermodynamics. Hence, we investigate the phase transitions occurring in the system and also obtain two tricritical points analytically. Finally, the specific heat and magnetic susceptibility are calculated and an argument about the critical exponents at the second-order phase transitions and tricritical points is given.
PHASE CHANGES IN NONLINEAR PROCESSES IN INTERACTING FOCK SPACE
Authors: DAS P. K. , GHOSH ARPITA
Published: February 2006

In this paper we study quantum mechanical phase distribution of some nonlinear optical phenomena in a general setting of interacting Fock space. We have investigated the optical phenomena of propagation through a nonlinear medium as in optical fiber and the process of photon absorption from a thermal beam. The input and output phase distribution have been investigated analytically in these two cases.
GRAVITATIONALLY-INDUCED PARTICLE RESORPTION INTO THE VACUUM: A GENERAL SOLUTION TO THE PROBLEM OF BLACK HOLE COLLAPSE
Authors: SILVERMAN M. P.
Published: February 2006

The process of gravitationally-induced particle creation (Hawking radiation), if it exists, necessitates, in accordance with general thermodynamic principles, a corresponding process of gravitationally-induced particle resorption into the vacuum. Although the former process occurs in the external vicinity of the Schwarzschild surface where matter density is relatively low, the latter process would be expected to occur inside the Schwarzschild surface where the stellar material is enormously compressed and fermions fill all quantum states up to the Fermi level. I show that the occurrence of particle resorption provides a general mechanism, irrespective of the interactions of the constituent particles, which halts the collapse of a black hole to a singular point and leads to an equilibrium state of macroscopic extent.
GRAVITY FROM A MODIFIED COMMUTATOR
Authors: JACKSON MARK G.
Published: February 2006

We show that a suitably chosen position-momentum commutator can elegantly describe many features of gravity, including the IR/UV correspondence and dimensional reduction ("holography"). Using the most simplistic example based on dimensional analysis of black holes, we construct a commutator which qualitatively exhibits these novel properties of gravity. Dimensional reduction occurs because the quanta size grow quickly with momenta, and thus cannot be "packed together" as densely as naively expected. We conjecture that a more precise form of this commutator should be able to quantitatively reproduce all of these features.
INFORMATION STORAGE IN BLACK HOLES
Authors: MAIA M. D.
Published: February 2006

The information loss paradox for Schwarzschild black holes is examined, using the ADS/CFT correspondence extended to the M6(4, 2) bulk. It is found that the only option compatible with the preservation of the quantum unitarity is when a regular remnant region of the black hole survives to the black hole evaporation process, where information can be stored and eventually retrieved.
THE COSMIC COINCIDENCE IN BRANS–DICKE COSMOLOGIES
Authors: CARNEIRO SAULO
Published: February 2006

Among the suggested solutions to the cosmological constant problem, we find the idea of a dynamic vacuum, with an energy density decaying with the universe expansion. We investigate the possibility of a variation in the gravitational constant as well, induced, at the cosmological scale, by the vacuum decay. We consider an effective Brans–Dicke theory in the spatially flat FLRW spacetime, finding late time solutions characterized by a constant ratio between the matter and vacuum energy densities. By using the observed limits for the universe age, we fix the only free parameter of our solutions, obtaining a relative matter density in the range 0.25<Ωm<0.4. In particular, for Ht = 1 we obtain Ωm= 1/3. This constitutes a possible explanation for another problem related to the cosmological term, the cosmic coincidence problem.
INFORMATION-PRESERVING BLACK HOLES STILL DO NOT PRESERVE BARYON NUMBER AND OTHER EFFECTIVE GLOBAL QUANTUM NUMBERS
Authors: STOJKOVIC DEJAN , STARKMAN GLENN D. , ADAMS FRED C.
Published: February 2006

It has been claimed recently that the black hole information-loss paradox has been resolved: the evolution of quantum states in the presence of a black hole is unitary and information preserving. We point out that, contrary to some claims in literature, information-preserving black holes still violate the baryon number and any other quantum number which follows from an effective (and thus approximate) or anomalous symmetry.
GRAVITY-WAVE DETECTORS AS PROBES OF EXTRA DIMENSIONS
Authors: CLARKSON CHRIS , MAARTENS ROY
Published: February 2006

If string theory is correct, then our observable universe may be a three-dimensional "brane" embedded in a higher-dimensional spacetime. This theoretical scenario should be tested via the state-of-the-art in gravitational experiments — the current and upcoming gravity-wave detectors. Indeed, the existence of extra dimensions leads to oscillations that leave a spectroscopic signature in the gravity-wave signal from black holes. The detectors that have been designed to confirm Einstein's prediction of gravity waves, can in principle also provide tests and constraints on string theory.
ENTROPY AND AREA IN LOOP QUANTUM GRAVITY
Authors: SWAIN JOHN
Published: February 2006

Black hole thermodynamics suggests that the maximum entropy that can be contained in a region of space is proportional to the area enclosing it rather than its volume. We argue that this follows naturally from loop quantum gravity and a result of Kolmogorov and Bardzin' on the the realizability of networks in three dimensions. This represents an alternative to other approaches in which some sort of correlation between field configurations helps limit the degrees of freedom within a region. It also provides an approach to thinking about black hole entropy in terms of states inside rather than on its surface. Intuitively, a spin network complicated enough to imbue a region with volume only lets that volume grow as quickly as the area bounding it.
EINSTEIN–PLANCK FORMULA, EQUIVALENCE PRINCIPLE, AND BLACK HOLE RADIANCE
Authors: FABBRI ALESSANDRO , NAVARRO-SALAS JOSE
Published: February 2006

The presence of gravity implies corrections to the Einstein–Planck formula E = hν. This gives hope that the divergent blueshift in frequency, associated to the presence of a black hole horizon, could be smoothed out for the energy. Using simple arguments based on Einstein's equivalence principle, we show that this is only possible if a black hole emits, in a first approximation, not just a single particle, but thermal radiation.
SIMPLE SOLUTIONS TO THE EINSTEIN EQUATIONS IN SPACES WITH UNUSUAL TOPOLOGY
Authors: BONDARESCU MIHAI
Published: February 2006

We discuss simple vacuum solutions to the Einstein Equations in five-dimensional space–times compactified in two different ways. In such spaces, one black hole phase and more than one black string phase may exist. Several old metrics are adapted to new background topologies to yield new solutions to the Einstein Equations. We then briefly talk about the angular momentum they may carry, the horizon topology and phase transitions that may occur.
THE EQUIVALENCE PRINCIPLE AS A PROBE FOR HIGHER DIMENSIONS
Authors: WESSON PAUL S.
Published: February 2006

Higher-dimensional theories of the kind which may unify gravitation with particle physics can lead to significant modifications of general relativity. In five dimensions, the vacuum becomes non-standard, and the Weak Equivalence Principle becomes a geometrical symmetry which can be broken, perhaps at a level detectable by new tests in space.
THE CASE FOR UNQUANTIZED GRAVITY
Authors: COOPERSTOCK F. I.
Published: February 2006

In this essay, we explore the hypothesis that gravity is best viewed as a non-quantized field, at least not in the usual sense of being quantized. It is linked to the energy localization hypothesis that energy, including the contribution from gravity, is localized in the region of the energy–momentum tensor. Evidence is gathered from among other aspects, the peculiar nature of gravitational plane waves and indirectly from the fact that there are no experimental results that point to a necessity for quantization. Should this hypothesis prove to be correct, it would favor the negation of the very existence of gravitons since gravitational waves would be seen as purely classical general relativistic constructs which carry no energy. Most significantly, unquantized gravity would turn the evidently unsolvable cosmological constant problem, viewed by various experts as the major crisis of modern physics, into a non-problem. In spite of this, there are indications to suggest that the study of limiting properties will lead to new insights into both the essence of space–time and the quantum world.
MINIMAL SPATIO-TEMPORAL EXTENT OF EVENTS, NEUTRINOS, AND THE COSMOLOGICAL CONSTANT PROBLEM
Authors: AHLUWALIA-KHALILOVA D. V.
Published: February 2006

Chryssomalakos and Okon, through a uniqueness analysis, have strengthened the Vilela Mendes suggestion that the immunity to infinitesimal perturbations in the structure constants of a physically-relevant Lie algebra should be raised to the status of a physical principle. Since the Poincaré–Heisenberg algebra does not carry the indicated immunity, it is suggested that the Lie algebra for the interface of the gravitational and quantum realms (IGQR) is its stabilized form. It carries three additional parameters: a length scale pertaining to the Planck/unification scale, a second length scale associated with cosmos, and a new dimensionless constant. Here, we show that the adoption of the stabilized Poincaré–Heisenberg algebra (SPHA) for the IGQR has the immediate implication that a "point particle" ceases to be a viable physical notion. It must be replaced by objects which carry a well-defined, representation space-dependent, minimal spatio-temporal extent. The ensuing implications have the potential, without spoiling any of the successes of the Standard Model of particle physics, to resolve the cosmological constant problem while concurrently offering a first-principle hint as to why there exists a coincidence between cosmic vacuum energy density and neutrino masses. The main theses which the essay presents is the following: an extension of the present-day physics to a framework which respects SPHA should be seen as the most natural and systematic path towards gaining a deeper understanding of outstanding questions, if not providing answers to them.
THE STRING COUPLING ACCELERATES THE EXPANSION OF THE UNIVERSE
Authors: ELLIS JOHN , MAVROMATOS NIKOLAOS E. , NANOPOULOS DIMITRI V.
Published: February 2006

Generic cosmological models in non-critical string theory have a time-dependent dilaton background at a late epoch. The cosmological deceleration parameter q0 is given by the square of the string coupling, [Formula: see text], up to a negative sign. Hence, the expansion of the universe must accelerate eventually, and the observed value of q0 corresponds to [Formula: see text]. In this scenario, the string coupling is asymptotically free at large times, but its present rate of change is imperceptibly small.
HORIZON MASS THEOREM
Authors: HA YUAN K.
Published: February 2006

A new theorem for black holes is found. It is called the horizon mass theorem. The horizon mass is the mass which cannot escape from the horizon of a black hole. For all black holes, neutral, charged or rotating, the horizon mass is always twice the irreducible mass observed at infinity. Previous theorems on black holes are: (i) the singularity theorem, (ii) the area theorem, (iii) the uniqueness theorem, (iv) the positive energy theorem. The horizon mass theorem is possibly the last general theorem for classical black holes. It is crucial for understanding Hawking radiation and for investigating processes occurring near the horizon.
BEYOND GRAVITOELECTROMAGNETISM: CRITICAL SPEED IN GRAVITATIONAL MOTION
Authors: MASHHOON BAHRAM
Published: February 2006

A null ray approaching a distant astronomical source appears to slow down, while a massive particle speeds up in accordance with Newtonian gravitation. The integration of these apparently incompatible aspects of motion in general relativity is due to the existence of a critical speed. The dynamics of particles moving faster than the critical speed could then be contrary to Newtonian expectations. Working within the framework of gravitoelectromagnetism, the implications of the existence of a critical speed are explored. The results are expected to be significant for high energy astrophysics.
AN AMBIGUOUS STATEMENT CALLED THE "TETRAD POSTULATE" AND THE CORRECT FIELD EQUATIONS SATISFIED BY THE TETRAD FIELDS
Authors: RODRIGUES WALDYR A. , SOUZA QUINTINO A. G.
Published: February 2006

The names tetrad, tetrads, cotetrads have been used with many different meanings in the physics literature, not all of them equivalent from the mathematical point of view. In this paper, we introduce unambiguous definitions for each of those terms, and show how the old miscellanea made many authors introduce in their formalism an ambiguous statement called the "tetrad postulate," which has been the source of much misunderstanding, as we show explicitly by examining examples found in the literature. Since formulating Einstein's field equations intrinsically in terms of cotetrad fields θa, a = 0, 1, 2, 3 is a worthy enterprise, we derive the equation of motion of each θausing modern mathematical tools (the Clifford bundle formalism and the theory of the square of the Dirac operator). Indeed, we identify (giving all details and theorems) from the square of the Dirac operator some noticeable mathematical objects, namely, the Ricci, Einstein, covariant D'Alembertian and the Hodge Laplacian operators, which permit us to show that each θasatisfies a well-defined wave equation. Also, we present for completeness a detailed derivation of the cotetrad wave equations from a variational principle. We compare the cotetrad wave equation satisfied by each θawith some others appearing in the literature, and which are unfortunately in error.
Introduction of Metoprolol Increases Plasma B-Type Cardiac Natriuretic Peptides in Mild, Stable Heart Failure
Authors: Davis Mark E. , Richards A. Mark , Nicholls M. Gary , Yandle Timothy G. , Frampton Christopher M. , Troughton Richard W.
Published: February 2006

Background—

The effect of β-blockade on the cardiac natriuretic peptides is poorly understood but could contribute to their beneficial treatment effect and may be relevant to clinical use of plasma brain natriuretic peptide (BNP)/N-terminal pro brain natriuretic peptide (NTproBNP) measurements in risk stratification and in titration of anti–heart failure therapy.

Methods and Results—

Sixteen men with mild, stable heart failure (NYHA class II to III; left ventricular ejection fraction <40%) underwent serial blood sampling for plasma natriuretic peptide levels and received infusions of atrial natriuretic peptide (ANP) and BNP before and 6 weeks after the introduction and uptitration of metoprolol or 6 weeks unchanged therapy in a randomized, parallel-group design. Plasma natriuretic peptides (BNP, NTproBNP, ANP, and NTproANP) were increased by metoprolol (
P
<0.01 for all). The natriuretic responses to ANP and BNP infusions were sustained with the introduction of metoprolol despite reduced renal perfusion pressure. The levels of the noninfused natriuretic peptide were increased by both ANP and BNP infusions, and this effect was enhanced by metoprolol. The early plasma half-life (t½α) of BNP was prolonged by metoprolol (5.6±0.45 to 11±1.3 versus 5.7±0.8 to 6.6±1.3 minutes in control subjects;
P
=0.019).

Conclusions—

Plasma cardiac natriuretic peptide levels increase significantly with the introduction of metoprolol in heart failure as a result of effects on secretion and clearance. Natriuretic responses to NP infusions are sustained with β-blockade despite reduced renal perfusion pressure. Clinicians should be aware that the introduction of metoprolol causes a rise in plasma BNP/NTproBNP that is unrelated to deterioration in clinical status and must be considered when measurements are undertaken for risk stratification or titration of treatment.
Novel Speckle-Tracking Radial Strain From Routine Black-and-White Echocardiographic Images to Quantify Dyssynchrony and Predict Response to Cardiac Resynchronization Therapy
Authors: Suffoletto Matthew S. , Dohi Kaoru , Cannesson Maxime , Saba Samir , Gorcsan John
Published: February 2006

Background—

Mechanical dyssynchrony is a potential means to predict response to cardiac resynchronization therapy (CRT). We hypothesized that novel echocardiographic image speckle tracking can quantify dyssynchrony and predict response to CRT.

Methods and Results—

Seventy-four subjects were studied: 64 heart failure patients undergoing CRT (aged 64±12 years, ejection fraction 26±6%, QRS duration 157±28 ms) and 10 normal controls. Speckle tracking applied to routine midventricular short-axis images calculated radial strain from multiple circumferential points averaged to 6 standard segments. Dyssynchrony from timing of speckle-tracking peak radial strain was correlated with tissue Doppler measures in 47 subjects (
r
=0.94,
P
<0.001; 95% CI 0.90 to 0.96). The ability of baseline speckle-tracking radial dyssynchrony (time difference in peak septal wall–to–posterior wall strain ≥130 ms) to predict response to CRT was then tested. It predicted an immediate increase in stroke volume in 48 patients studied the day after CRT with 91% sensitivity and 75% specificity. In 50 patients with long-term follow-up 8±5 months after CRT, baseline speckle-tracking radial dyssynchrony predicted a significant increase in ejection fraction with 89% sensitivity and 83% specificity. Patients in whom left ventricular lead position was concordant with the site of latest mechanical activation by speckle-tracking radial strain had an increase in ejection fraction from baseline to a greater degree (10±5%) than patients with discordant lead position (6±5%;
P
<0.05).

Conclusions—

Speckle-tracking radial strain can quantify dyssynchrony and predict immediate and long-term response to CRT and has potential for clinical application.
Biventricular Pacing Improves the Blunted Force–Frequency Relation Present During Univentricular Pacing in Patients With Heart Failure and Conduction Delay
Authors: Vollmann Dirk , Lüthje Lars , Schott Peter , Hasenfuss Gerd , Unterberg-Buchwald Christina
Published: February 2006

Background—

In patients with chronic heart failure (CHF) and conduction delay, biventricular (BiV) and left ventricular (LV) pacing similarly improve systolic function at resting heart rates. We hypothesized that BiV and univentricular pacing differentially affect contractile function at increasing heart rates.

Methods and Results—

Twenty-two patients (aged 66±2 years, QRS 179±8 ms, LV ejection fraction 23±1%) underwent cardiac catheterization before device implantation to measure LV hemodynamics at baseline (rate 68±2 bpm; sinus rhythm n=18; atrial fibrillation n=4) and during BiV, LV, and right ventricular (RV) stimulation at 80, 100, 120, and 140 bpm. BiV and LV pacing at 80 bpm equally augmented dP/dt
max
as compared with baseline and RV pacing (
P
<0.001). Stimulation rate significantly interacted with the effect of BiV, LV, and RV pacing on LV end-diastolic pressure (LVEDP), systolic pressure (LVSP), and dP/dt
max
. Increasing the rate from 80 to 140 bpm enhanced dP/dt
max
from 913±28 to 1119±50 mm Hg/s during BiV stimulation (
P
<0.001) but had no significant effect on contractility during single-site LV (951±47 versus 1002±54 mm Hg/s) or RV (800±46 versus 881±49 mm Hg/s) pacing. At 140 bpm, LVEDP was lower and LVSP higher during BiV pacing than during RV and LV pacing (LVEDP 12±1 versus 17±1 and 16±1 mm Hg,
P
<0.001; LVSP 112±5 versus 106±5 and 108±6 mm Hg,
P
<0.01 and
P
=0.09; BiV versus RV and LV pacing, respectively).

Conclusions—

Different modes of ventricular stimulation alter the in vivo force–frequency relation of CHF patients. In contrast to single-site LV and RV pacing, contractile function improves with increasing heart rates during BiV stimulation. This effect may contribute to the enhanced exercise capacity during BiV pacing and could provide a functional benefit over LV-only pacing in patients for whom resynchronization therapy is indicated.
Cross-Sectional Relations of Multiple Biomarkers From Distinct Biological Pathways to Brachial Artery Endothelial Function
Authors: Kathiresan Sekar , Gona Philimon , Larson Martin G. , Vita Joseph A. , Mitchell Gary F. , Tofler Geoffrey H. , Levy Daniel , Newton-Cheh Christopher , Wang Thomas J. , Benjamin Emelia J. , Vasan Ramachandran S.
Published: February 2006

Background—

Endothelial dysfunction is a critical intermediate phenotype in the pathogenesis of cardiovascular disease. We evaluated the relative contributions of distinct biological pathways to interindividual variation in endothelial function by relating prototype biomarkers (representing these pathways) to brachial artery vasodilator function.

Methods and Results—

We investigated the cross-sectional relations of a panel of 7 biomarkers measured at a routine examination to brachial artery vasodilator function (flow-mediated dilation [FMD] and reactive hyperemia) assessed at a subsequent examination (mean interval, 2.9 years) in 2113 Framingham Heart Study participants (mean age, 61 years; 54% women). We selected biomarkers from 4 biological domains: neurohormonal (N-terminal pro-atrial natriuretic peptide [N-ANP], B-type natriuretic peptide [BNP], renin, aldosterone), hemostatic factors (plasminogen activator inhibitor-1 [PAI-1]), inflammation (C-reactive protein [CRP]), and target organ damage (urine albumin-creatinine ratio). In age- and sex-adjusted models, several biomarkers were related to baseline brachial artery diameter (PAI-1, CRP, urine albumin-creatinine ratio), baseline mean flow (N-ANP, BNP, PAI-1, CRP, aldosterone), FMD (N-ANP, PAI-1, CRP, renin), and reactive hyperemia (BNP, PAI-1, CRP, renin, urine albumin-creatinine ratio). In multivariable analyses relating the 7 biomarkers conjointly to each vascular function measure (adjusting for known risk factors), N-ANP and renin were positively related to FMD (
P
=0.001 and
P
=0.04, respectively), and N-ANP was inversely related to baseline mean flow velocity (
P
=0.01). None of the other biomarkers was significantly related to the vascular function measures studied.

Conclusions—

In our large community-based sample, a conservative strategy relating several biomarkers to vascular endothelial function identified plasma N-ANP as a key correlate of mean flow under basal conditions and of FMD in response to forearm cuff occlusion.
Clinical Correlates and Consequences of Anemia in a Broad Spectrum of Patients With Heart Failure
Authors: O’Meara Eileen , Clayton Tim , McEntegart Margaret B. , McMurray John J.V. , Lang Chim C. , Roger Simon D. , Young James B. , Solomon Scott D. , Granger Christopher B. , Östergren Jan , Olofsson Bertil , Michelson Eric L. , Pocock Stuart , Yusuf Salim , Swedberg Karl , Pfeffer Marc A.
Published: February 2006

Background—

We wished to determine the prevalence of, potential mechanistic associations of, and clinical outcomes related to anemia in patients with heart failure and a broad spectrum of left ventricular ejection fraction (LVEF).

Methods and Results—

In multivariable analyses, we examined the associations between hemoglobin and baseline characteristics, laboratory variables, and outcomes in 2653 patients randomized in the CHARM Program in the United States and Canada. Anemia was equally common in patients with preserved (27%) and reduced (25%) LVEF but was more common in black and older patients. Anemia was associated with ethnicity, diabetes, low body mass index, higher systolic and lower diastolic blood pressure, and recent heart failure hospitalization. More than 50% of anemic patients had a glomerular filtration rate <60 mL · min
−1
· 1.73 m
−2
compared with <30% of nonanemic patients. Despite an inverse relationship between hemoglobin and LVEF, anemia was associated with an increased risk of death and hospitalization, a relationship observed in patients with both reduced and preserved LVEF. There were 133 versus 69 deaths and 527 versus 352 hospitalizations per 1000 patient-years of follow-up in anemic versus nonanemic patients (both
P
<0.001). The effect of candesartan in reducing outcomes was independent of hemoglobin.

Conclusions—

Anemia was common in heart failure, regardless of LVEF. Lower hemoglobin was associated with higher LVEF yet was an independent predictor of adverse mortality and morbidity outcomes. In heart failure, the causes of anemia and the associations between anemia and outcomes are probably multiple and complex.
In Vivo Visualization of Embryonic Stem Cell Survival, Proliferation, and Migration After Cardiac Delivery
Authors: Cao Feng , Lin Shuan , Xie Xiaoyan , Ray Pritha , Patel Manishkumar , Zhang Xianzhong , Drukker Micha , Dylla Scott J. , Connolly Andrew J. , Chen Xiaoyuan , Weissman Irving L. , Gambhir Sanjiv S. , Wu Joseph C.
Published: February 2006

Background—

Recent studies have shown that stem cell therapy can promote tissue regeneration; however, monitoring stem cells in vivo remains problematic owing to limitations of conventional histological assays and imaging modalities.

Methods and Results—

Murine embryonic stem (ES) cells were stably transduced with a lentiviral vector carrying a novel triple-fusion (TF) reporter gene that consists of firefly luciferase, monomeric red fluorescence protein, and truncated thymidine kinase (fluc-mrfp-ttk). ES cell viability, proliferation, and differentiation ability were not adversely affected by either reporter genes or reporter probes compared with nontransduced control cells (
P
=NS). Afterward, 1×10
7
of ES cells carrying the TF reporter gene (ES-TF) were injected into the myocardium of adult nude rats (n=20). Control animals received nontransduced ES cells (n=6). At day 4, the bioluminescence and positron emission tomography signals in study animals were 3.7×10
7
±5.8×10
6
photons · s
−1
· cm
−2
per steradian (sr) and 0.08±0.03% injected dose/g, respectively (
P
<0.05 versus control). Both signals increased progressively from week 1 to week 4, which indicated ES cell survival and proliferation in the host. Histological analysis demonstrated the formation of intracardiac and extracardiac teratomas. Finally, animals (n=4) that were treated with intraperitoneal injection of ganciclovir (50 mg/kg) did not develop teratomas when compared with control animals (n=4) treated with saline (1 mL/kg).

Conclusion—

This is the first study to characterize ES cells that stably express fluorescence, bioluminescence, and positron emission tomography reporter genes and monitor the kinetics of ES cell survival, proliferation, and migration. This versatile imaging platform should have broad applications for basic research and clinical studies on stem cell therapy.
Differential Impact of Blood Pressure–Lowering Drugs on Central Aortic Pressure and Clinical Outcomes
Authors:   The CAFE Investigators,   CAFE Steering Committee and Writing Committee, Williams Bryan , Lacy Peter S. , Thom Simon M. , Cruickshank Kennedy , Stanton Alice , Collier David , Hughes Alun D. , Thurston H. , O’Rourke Michael
Published: February 2006

Background—

Different blood pressure (BP)–lowering drugs could have different effects on central aortic pressures and thus cardiovascular outcome despite similar effects on brachial BP. The Conduit Artery Function Evaluation (CAFE) study, a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), examined the impact of 2 different BP lowering-regimens (atenolol±thiazide-based versus amlodipine±perindopril-based therapy) on derived central aortic pressures and hemodynamics.

Methods and Results—

The CAFE study recruited 2199 patients in 5 ASCOT centers. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressures and hemodynamic indexes on repeated visits for up to 4 years. Most patients received combination therapy throughout the study. Despite similar brachial systolic BPs between treatment groups (Δ0.7 mm Hg; 95% CI, −0.4 to 1.7;
P
=0.2), there were substantial reductions in central aortic pressures with the amlodipine regimen (central aortic systolic BP, Δ4.3 mm Hg; 95% CI, 3.3 to 5.4;
P
<0.0001; central aortic pulse pressure, Δ3.0 mm Hg; 95% CI, 2.1 to 3.9;
P
<0.0001). Cox proportional-hazards modeling showed that central pulse pressure was significantly associated with a post hoc–defined composite outcome of total cardiovascular events/procedures and development of renal impairment in the CAFE cohort (unadjusted,
P
<0.0001; adjusted for baseline variables,
P
<0.05).

Conclusions—

BP-lowering drugs can have substantially different effects on central aortic pressures and hemodynamics despite a similar impact on brachial BP. Moreover, central aortic pulse pressure may be a determinant of clinical outcomes, and differences in central aortic pressures may be a potential mechanism to explain the different clinical outcomes between the 2 BP treatment arms in ASCOT.
An Ocean Refractometer: Resolving Millimeter-Scale Turbulent Density Fluctuations via the Refractive Index
Authors: Alford Matthew H. , Gerdt David W. , Adkins Charles M.
Published: February 2006

A fiberoptic sensor has been constructed to measure oceanic density fluctuations via their refractive index signature. The resolution (Δz = 1 mm, Δt = 0.2 ms) and precision (Δn < 10−8, Δρ = 3.4 × 10−5 kg m−3) of the device are far better than other methods and are sufficient to resolve the entire turbulent spectrum. Spectra show the salinity Batchelor rolloff at levels undetectable via conductivity measurements. However, the low-wavenumber portion of the spectrum occupied by the turbulent inertial subrange (≈1 m–1 cm scales) is marred by noise resulting from fiber motion in response to turbulent velocity fluctuations. The technique is described, and the first ocean measurements are reported.
A New Portable Instrument for Continuous Measurement of Formaldehyde in Ambient Air
Authors: Junkermann W. , Burger J. M.
Published: February 2006

A new instrument for the in situ measurement of formaldehyde with online concentration output was built on the base of the Hantzsch chemistry fluorimetric detection of formaldehyde in liquid phase. The instrument was specially designed for applications in a fast-changing environment, for example, in airborne research. Individual instrument components were optimized to reduce size, weight, and power consumption and to improve response time. The small size, battery-operated system was shown to reach good performance, stable sensitivity, and detection limits of <100 ppt for temperatures between 0° and 35°C during aircraft flight missions in field campaigns in the Italian Po Valley. The instrument proved its performance with formaldehyde mixing ratios ranging from 0.5 to 25 ppb.
Evaluation of a Triple-Axis Coherent Doppler Velocity Profiler for Measuring Near-Bed Flow: A Field Study
Authors: Betteridge K. F. E. , Bell P. S. , Thorne P. D. , Williams J. J.
Published: February 2006

Collocated detailed measurements of near-bed turbulent and intrawave flow are important for studying sediment transport processes and seabed evolution. Existing commercially available triple-axis profiling instruments do not provide collocated velocity measurements. To improve the capability to make such measurements a triple-axis coherent Doppler velocity profiler (CDVP) has been developed and tested in the marine environment. The instrument was designed to measure orthogonal velocity profiles within a narrow column of water at 16 Hz within 1 m of the bed with a vertical spatial resolution of 0.05 m. This paper describes the first deployment of the instrument, in a tidal inlet in Portugal during a multidisciplinary study, when CDVP flow velocity measurements were compared with data from other instrumentation. A pragmatic approach was adopted to assess the capability of the triple-axis CDVP, using both an evaluation of internal consistency and an assessment against two commercially available acoustic Doppler velocimeters (ADVs). Measurements of the mean and fluctuating velocity profiles were collected with the triple-axis CDVP, and these have been shown to be internally consistent and to be in good agreement with measurements obtained with the ADVs.
The Shift in Academic Quality Control
Authors: Hemlin Sven , Rasmussen Søren Barlebo
Published: February 2006

Quality control is an important and integrated part of the scientific system. However, developments in science and society are changing quality control into quality monitoring. New, virtual, and fluid organizational forms are emerging. Common boundaries are seen as being broken down as, for example, in the “triple helix” and the “mode 2” concepts. The stakeholders in science are showing an interest in being more involved in science. They want their evaluation criteria to be used, and they want evaluations to be done on a regular basis because they do not trust the new scientific institutions to be left on their own. Quality monitoring changes the requirements for conducting evaluations as part of quality control. Assessing the societal value of research becomes increasingly important. Finally, quality monitoring emphasizes organizational learning rather than controlling quality in scientific organizations.