Resonant quantum transitions in trapped antihydrogen atoms.

The hydrogen atom is one of the most important and influential model systems in modern physics. Attempts to understand its spectrum are inextricably linked to the early history and development of quantum mechanics. The hydrogen atom's stature lies in its simplicity and in the accuracy with which its spectrum can be measured and compared to theory. Today its spectrum remains a valuable tool for determining the values of fundamental constants and for challenging the limits of modern physics, including the validity of quantum electrodynamics and--by comparison with measurements on its antimatter counterpart, antihydrogen--the validity of CPT (charge conjugation, parity and time reversal) symmetry. Here we report spectroscopy of a pure antimatter atom, demonstrating resonant quantum transitions in antihydrogen. We have manipulated the internal spin state of antihydrogen atoms so as to induce magnetic resonance transitions between hyperfine levels of the positronic ground state. We used resonant microwave radiation to flip the spin of the positron in antihydrogen atoms that were magnetically trapped in the ALPHA apparatus. The spin flip causes trapped anti-atoms to be ejected from the trap. We look for evidence of resonant interaction by comparing the survival rate of trapped atoms irradiated with microwaves on-resonance to that of atoms subjected to microwaves that are off-resonance. In one variant of the experiment, we detect 23 atoms that survive in 110 trapping attempts with microwaves off-resonance (0.21 per attempt), and only two atoms that survive in 103 attempts with microwaves on-resonance (0.02 per attempt). We also describe the direct detection of the annihilation of antihydrogen atoms ejected by the microwaves.

Allelopathic interference of alfalfa (Medicago sativa L.) genotypes to annual ryegrass (Lolium rigidum).

Alfalfa (Medicago sativa L.) genotypes at varying densities were investigated for allelopathic impact using annual ryegrass (Lolium rigidum) as the target species in a laboratory bioassay. Three densities (15, 30, and 50 seedlings/beaker) and 40 alfalfa genotypes were evaluated by the equal compartment agar method (ECAM). Alfalfa genotypes displayed a range of allelopathic interference in ryegrass seedlings, reducing root length from 5 to 65%. The growth of ryegrass decreased in response to increasing density of alfalfa seedlings. At the lowest density, Q75 and Titan9 were the least allelopathic genotypes. An overall inhibition index was calculated to rank each alfalfa genotype. Reduction in seed germination of annual ryegrass occurred in the presence of several alfalfa genotypes including Force 10, Haymaster7 and SARDI Five. A comprehensive metabolomic analysis using Quadruple Time of Flight (Q-TOF), was conducted to compare six alfalfa genotypes. Variation in chemical compounds was found between alfalfa root extracts and exudates and also between genotypes. Further individual compound assessments and quantitative study at greater chemical concentrations are needed to clarify the allelopathic activity. Considerable genetic variation exists among alfalfa genotypes for allelopathic activity creating the opportunity for its use in weed suppression through selection.

Trapped antihydrogen.

Antimatter was first predicted in 1931, by Dirac. Work with high-energy antiparticles is now commonplace, and anti-electrons are used regularly in the medical technique of positron emission tomography scanning. Antihydrogen, the bound state of an antiproton and a positron, has been produced at low energies at CERN (the European Organization for Nuclear Research) since 2002. Antihydrogen is of interest for use in a precision test of nature's fundamental symmetries. The charge conjugation/parity/time reversal (CPT) theorem, a crucial part of the foundation of the standard model of elementary particles and interactions, demands that hydrogen and antihydrogen have the same spectrum. Given the current experimental precision of measurements on the hydrogen atom (about two parts in 10(14) for the frequency of the 1s-to-2s transition), subjecting antihydrogen to rigorous spectroscopic examination would constitute a compelling, model-independent test of CPT. Antihydrogen could also be used to study the gravitational behaviour of antimatter. However, so far experiments have produced antihydrogen that is not confined, precluding detailed study of its structure. Here we demonstrate trapping of antihydrogen atoms. From the interaction of about 10(7) antiprotons and 7 × 10(8) positrons, we observed 38 annihilation events consistent with the controlled release of trapped antihydrogen from our magnetic trap; the measured background is 1.4 ± 1.4 events. This result opens the door to precision measurements on anti-atoms, which can soon be subjected to the same techniques as developed for hydrogen.

A Mathematical Model of Granulopoiesis Incorporating the Negative Feedback Dynamics and Kinetics of G-CSF/Neutrophil Binding and Internalization.

We develop a physiological model of granulopoiesis which includes explicit modelling of the kinetics of the cytokine granulocyte colony-stimulating factor (G-CSF) incorporating both the freely circulating concentration and the concentration of the cytokine bound to mature neutrophils. G-CSF concentrations are used to directly regulate neutrophil production, with the rate of differentiation of stem cells to neutrophil precursors, the effective proliferation rate in mitosis, the maturation time, and the release rate from the mature marrow reservoir into circulation all dependent on the level of G-CSF in the system. The dependence of the maturation time on the cytokine concentration introduces a state-dependent delay into our differential equation model, and we show how this is derived from an age-structured partial differential equation model of the mitosis and maturation and also detail the derivation of the rest of our model. The model and its estimated parameters are shown to successfully predict the neutrophil and G-CSF responses to a variety of treatment scenarios, including the combined administration of chemotherapy and exogenous G-CSF. This concomitant treatment was reproduced without any additional fitting to characterize drug-drug interactions.

Autoresonant excitation of antiproton plasmas.

We demonstrate controllable excitation of the center-of-mass longitudinal motion of a thermal antiproton plasma using a swept-frequency autoresonant drive. When the plasma is cold, dense, and highly collective in nature, we observe that the entire system behaves as a single-particle nonlinear oscillator, as predicted by a recent theory. In contrast, only a fraction of the antiprotons in a warm plasma can be similarly excited. Antihydrogen was produced and trapped by using this technique to drive antiprotons into a positron plasma, thereby initiating atomic recombination.

Centrifugal separation and equilibration dynamics in an electron-antiproton plasma.

Charges in cold, multiple-species, non-neutral plasmas separate radially by mass, forming centrifugally separated states. Here, we report the first detailed measurements of such states in an electron-antiproton plasma, and the first observations of the separation dynamics in any centrifugally separated system. While the observed equilibrium states are expected and in agreement with theory, the equilibration time is approximately constant over a wide range of parameters, a surprising and as yet unexplained result. Electron-antiproton plasmas play a crucial role in antihydrogen trapping experiments.

Evaporative cooling of antiprotons to cryogenic temperatures.

We report the application of evaporative cooling to clouds of trapped antiprotons, resulting in plasmas with measured temperature as low as 9 K. We have modeled the evaporation process for charged particles using appropriate rate equations. Good agreement between experiment and theory is observed, permitting prediction of cooling efficiency in future experiments. The technique opens up new possibilities for cooling of trapped ions and is of particular interest in antiproton physics, where a precise CPT test on trapped antihydrogen is a long-standing goal.

Different conformations of the German shepherd dog breed affect its posture and movement.

The conformation of the German shepherd dog (GSD) varies considerably within the breed. These differences may result in large variation in the movement and limb loading and undesirable consequences to their musculoskeletal health. This study aimed to investigate the relationship between conformation and biomechanical measures in 60 GSDs. Full body kinematic and kinetic measures were computed from 3D motion capture and pressure data. The dogs were divided into groups based on their back slope and curvature. Correlation analysis and statistical differences between groups showed that GSDs with a greater back slope have a greater contact area in their forelimbs and place them closer together when standing (n = 60). During trot, the dogs with sloped back showed a greater vertical force in the forelimbs and a greater mid-thoracic flexion (n = 60). Unilateral differences were found in the stifle flexion, hock flexion and hock adduction, suggesting greater movement asymmetry with an increase in the back slope (n = 30). In conclusion, several biomechanical parameters are affected by the GSD's slope of the back and not by its curvature. Further studies are required to determine whether the variation in movement, posture and conformation within the breed relates to an increased susceptibility to musculoskeletal disorders.

Tissue-specific transgenic knockdown of Fos-related antigen 2 (Fra-2) expression mediated by dominant negative Fra-2.

Fos-related antigen 2 (Fra-2) is a member of the Fos family of immediate-early genes, most of which are rapidly induced by second messengers. All members of this family act by binding to AP-1 sites as heterodimeric complexes with other proteins. However, each appears to have a distinct role. The role and biology of Fra-2 are less well understood than those of its relatives c-Fos, Fra-1, and FosB; moreover, Fra-2 target genes remain largely unknown, as does the basis of its selective effects on transcriptional activity. To pursue these issues, we created a transgenic rat line (NATDNF2) in which a dominant negative fra-2 (DNF2) gene is strongly expressed in the pineal gland; tissue selectivity was achieved by putting the DNF2 gene under the control of the rat arylalkylamine N-acetyltransferase (AANAT) regulatory region, which targets gene expression to a very restricted set of tissues (pineal gland >> retina). Expression of AANAT is normally turned on after the onset of darkness in the rat; as a result, pineal DNF2 expression occurs only at night. This was associated with marked suppression of the nocturnal increase in fra-2 mRNA and protein levels, indicating that DNF2 expression inhibits downstream effects of Fra-2, including the maintenance of high levels of fra-2 gene expression. Analysis of 1,190 genes in the NATDNF2 pineal gland, including the AANAT gene, identified two whose expression is strongly linked to fra-2 expression: the genes encoding type II iodothyronine deiodinase and nectadrin (CD24).

Method of preservation is not a determinant of graft outcome in kidneys transplanted by Southeastern Organ Procurement Foundation Institutions.

We report the observation that the major sources of variation in cadaver renal allograft survival rates are not related to the technique of donor organ preservation but are related solely to other factors including pretransplant blood transfusion of the recipient, antilymphocyte serum (ALS) treatment of the recipient, and high HLA match. In contrast to prior studies which used univariate methods to analyze similar data, our analysis shows that it is imperative that comparisons of different methods of cadaver preservation must include adjustments for the effects of pretransplant blood transfusions, antilymphocyte serum, and HLA match.

Increasing the supply of cadaveric kidneys for transplantation.

The number of cadaveric kidneys currently available for transplantation is insufficient. Therefore, the Center for Disease Control (CDC) undertook a collaborative project with the two transplant programs in Georgia to increase te retrieval of cadaveric kidneys. We used retrospective analysis to select productive hospitals, hospital-specific surveillance systems to identify potential donors, and procurement and retrieval evaluation to identify preventable deficiencies. During 900 hospital months of prospective surveillance, we identified a total of 555 potential donors by death record review, giving a potential donor rate of 2.3 donors/100 deaths (110 kidneys/million population/year). We observed an increase in the number of referrals, consent obtained from next of kin, and kidneys retrieved. This period of intensive activity demonstrated that additional kidneys can be retrieved by using systematic methods.

cDNA array analysis of pineal gene expression reveals circadian rhythmicity of the dominant negative helix-loop-helix protein-encoding gene, Id-1.

The pineal gland is a major output of the endogenous vertebrate circadian clock, with melatonin serving as the output signal. In many species, elevated nocturnal melatonin production is associated with changes in pineal gene expression. In the current study, cDNA array analysis was used in an attempt to identify additional genes that exhibit day/night differential expression in the rat pineal gland. This revealed 38 candidate genes, including Id-1 (inhibitor of DNA binding and differentiation). Id-1 encodes a helix-loop-helix (HLH) protein that lacks a basic DNA binding domain and could affect pineal physiology via a dominant negative trans-acting regulatory activity. For this reason Id-1 was selected for further analysis. Id-1 was expressed in a major population of pineal cells and the Id-1 protein was associated with a nuclear complex. The levels of Id-1 mRNA and protein exhibit approximately six-fold day/night rhythms. In contrast, the related genes Id-2 and Id-3 do not exhibit marked day/night differences in pineal expression. Rhythmic Id-1 expression is primarily limited to a C-terminally extended splice variant of Id-1, which would restrict the functional output of the rhythm to protein binding partners of this isoform of Id-1. Our findings add to the body of evidence indicating that transcriptional regulators play a role in neuroendocrine rhythms, and extend this by introducing the concept of a dominant negative HLH involvement. The rhythm in Id-1 in the pineal gland provides an experimental opportunity to identify Id-1-binding partners which may also be involved in Id-1 activity in other functional contexts.

Unoperated, asymptomatic significant internal carotid artery stenosis: a review of 182 instances.

One hundred and sixty-eight asymptomatic patients with a carotid artery stenosis of more than 50% were observed over a period of up to 12 years. During this time, 136 patients remained asymptomatic, two patients developed atypical neurologic symptoms that spontaneously disappeared, 26 patients developed transient ischemic attacks and successfully underwent carotid endarterectomy, three patients developed transient ischemic attacks that were ignored and they subsequently suffered a completed stroke, and one patient suffered a completed stroke without a warning transient attack. These data suggest that surgery is not required in the patient with an asymptomatic carotid stenosis until a transient ischemic attack occurs.

Optimisation of methods for selecting candidate genes from cDNA array screens: application to rat brain punches and pineal.

DNA arrays are potentially powerful experimental tools within neuroscience but application of this technology to in vivo paradigms may, in practice, be limited by the sensitivity of transcript detection and inter-screen variation. Here we describe the use of brain punch micro-sampling, used in combination with commercially available cDNA arrays, for profiling brain gene expression in a mutant strain of rat (GAERS model of absence epilepsy). Furthermore, we describe a multi-step optimisation of analysis methods which provides for improved sensitivity and absence of bias in the selection of candidate genes which may be differentially expressed in the mutant. Our method has been validated through application to a second paradigm, rhythmic gene expression in the rat pineal gland. Our experimental design, and analysis method should therefore be generally applicable to subtle discriminations of transcript abundance within discrete brain areas.

Familial exudative vitreoretinopathy linked to D11S533 in a large Asian family with consanguinity.

Familial exudative vitreoretinopathy (FEVR) is a disorder characterised by peripheral retinal vascularisation with subsequent traction of retinal vessels and detachment. Recently, autosomal dominant FEVR (ad FEVR) has been mapped to 11q13 by linkage in four northern European families. We describe a large consanguineous Asian family in which the severity of the proband's eye disease suggested homozygosity for a disease allele. Thirty family members were assessed by ophthalmological examination and fluorescein angiography. Thirteen had unequivocal features of FEVR. A further two were classified as unknown. Two point linkage analysis for DIIS533 and FEVR generated a lod score of 5.55 at a recombination fraction of 0.00. This supports autosomal dominant inheritance and demonstrates genetic homogeneity for the ad FEVR disease locus. The severely affected proband was heterozygous for alleles at this closely linked locus. Other causes, including non-genetic factors, should be considered to explain the extreme variability characteristic of ad FEVR.

The feasibility of replacement therapy for inherited disorder of glycolysis: triosephosphate isomerase deficiency (review).

Triosephosphate isomerase (TPI, EC 5.3.1.1) is an ubiquitously expressed enzyme that catalyses the interconversion of dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate in the energy-generating glycolytic pathway. Inherited defects in the TPI gene are characterised biochemically by markedly reduced TPI enzyme activity in all tissues resulting in metabolic block in glycolysis, with accumulating DHAP particularly in red cells. Clinical TPI deficiency is a rare autosomal recessive multi-system disorder characterised by non-spherocytic haemolytic anaemia, recurrent infections, cardiomyopathy, severe and fatal neuromuscular dysfunctions. Reviews of current literature show that after 30 years since TPI deficiency was first described, the disease still remains without effective therapy. However, several potential therapeutic strategies exist for the treatment of inherited metabolic disorders such as TPI deficiency. Development of an effective therapy for TPI deficiency presents a fascinating and formidable challenge for basic laboratory and clinical research. The major aim of this overview is to discuss the current knowledge of TPI deficiency with special emphasis on research efforts directed towards reversing the metabolic effects of the disorder.

Regulation of triosephosphate isomerase (TPI) gene expression in TPI deficient lymphoblastoid cells.

The metabolic defect of triosephosphate isomerase (TPI) deficiency is reversible in deficient lymphoblastoid cells when cultured in the presence of human K562 erythroleukemia cells or plasma as exogenous source of functional enzyme. However, plasma contains a variety of undefined biological response modifiers whose effects on TPI gene expression are unknown. In the present study, TPI deficient lymphoblastoid cells were cultured in serum-free medium for 24 h (controls) and stimulated with fresh frozen plasma (FFP) at final concentrations of 20, 40, and 60% for 9 h. Changes in TPI mRNA expression were monitored by slot and Northern blot hybridisations using a specific human TPI cDNA probe. For equivalent loading of total RNA, TPI mRNA expression in FFP-treated lymphoblastoid cells exceeded that for controls by on average 20-fold. Additional studies with the transcription inhibitor, actinomycin D, revealed a rapid degradation of TPI mRNA in controls compared to FFP-treated cells, indicating that the stability of the TPI transcript was affected by plasma. These data suggest that functional or regulatory elements within the TPI gene promoter can be modulated by biological response modifiers. An understanding of the transcriptional control of TPI may provide useful insights into the development of gene therapy strategies for TPI deficiency.

Elevated basilic vein arteriovenous fistula.

BACKGROUND: Many surgeons continue to use prosthetic arteriovenous grafts for dialysis access despite the clear superiority of native arteriovenous fistulas. This study was undertaken to review our experience with elevated brachial-basilic fistulas as an alternative to prosthetic grafts in patients lacking veins suitable for more conventional arteriovenous fistulas. METHODS: We retrospectively reviewed the outcomes of 67 patients receiving elevated brachial-basilic arteriovenous fistulas over a 10-year period. Operative complications and causes of failure were identified and actuarial fistula patency determined. RESULTS: No patients suffered wound infections, and only 1 developed a steal syndrome in the late postoperative period. Actuarial fistula patency was 84% at 1 year, 73% at 3 and 5 years, and 52% at 10 years. CONCLUSIONS: The elevated brachial-basilic arteriovenous fistula is a superb alternative to prosthetic arteriovenous grafts in patients lacking suitable cephalic veins for native arteriovenous fistulas. Operative complications are uncommon, vascular steal is rare, and long-term patency is excellent.

The jelly envelopes and fertilization of eggs of the newt, Notophthalmus viridescens.

Fertilization in Notophthalmus viridescens is internal and involves passage of the sperm through five layers of egg jelly (J5-J1, from outermost to innermost), each of which is secreted by a discrete region of the oviduct. Polyspermy is normal. Passage of the sperm through the jelly and into the egg was studied by a technique of artificial insemination similar to natural insemination, in that undiluted fluid from the vas deferens was applied directly to eggs with various layers of jelly present, followed by flooding with water three to five minutes later. In general, successful fertilization increased as the number of jelly layers increased; jellyless coelomic eggs were not fertilizable. Sperm passage through the jelly and into the egg usually occurs within one to three minutes. Upon hydration of the jelly, barriers to sperm penetration develop in layers J5 and J3. Changes in the egg jelly thus seem to be involved in the restriction of polyspermy to a low level.

Acute intestinal ischemia.

The present mortality rate of more than 80% for patients with superior mesenteric arterial thrombosis or embolism will remain unacceptable until earlier diagnosis is achieved. Although leukocytosis is often an early feature and may seem elevated out of proportion to the severity of the illness, the later developments of abdominal rigidity, intestinal paralysis, and vascular collapse indicate transmural gangrene and peritonitis. At this stage, the eventual high mortality of acute ischemia is established whatever the urgency of the operation or the skill with which it is performed. The syndrome must be suspected immediately when a patient in an older age group complains of sudden abdominal pain in the presence of associated cardiac arrhythmia, valvular disease or congestive heart failure, particularly if other sites of peripheral embolization are identified.