A Bragg glass phase in the vortex lattice of a type II superconductor

Although crystals are usually quite stable, they are sensitive to a disordered environment: even an infinitesimal amount of impurities can lead to the destruction of the crystalline order. The resulting state of matter has been a longstanding puzzle. Until recently it was believed to be an amorphous state in which the crystal would break into crystallites. But a different theory predicts the existence of a novel phase of matter: the so-called Bragg glass, which is a glass and yet nearly as ordered as a perfect crystal. The lattice of vortices that can contain magnetic flux in type II superconductors provide a good system to investigate these ideas. Here we show that neutron diffraction data of the vortex lattice in type II superconductors provides unambiguous evidence for a weak, power-law decay of the crystalline order characteristic of a Bragg glass. The theory also predicts accurately the electrical transport properties of superconductors; it naturally explains the observed phase transition and the dramatic jumps in the critical current associated with the melting of the Bragg glass. Moreover the model explains experiments as diverse as X-ray scattering in disordered liquid crystals and conductivity of electronic crystals.Comment: 9 pages, 4 figure

Some methods for blindfolded record linkage

BACKGROUND: The linkage of records which refer to the same entity in separate data collections is a common requirement in public health and biomedical research. Traditionally, record linkage techniques have required that all the identifying data in which links are sought be revealed to at least one party, often a third party. This necessarily invades personal privacy and requires complete trust in the intentions of that party and their ability to maintain security and confidentiality. Dusserre, Quantin, Bouzelat and colleagues have demonstrated that it is possible to use secure one-way hash transformations to carry out follow-up epidemiological studies without any party having to reveal identifying information about any of the subjects – a technique which we refer to as "blindfolded record linkage". A limitation of their method is that only exact comparisons of values are possible, although phonetic encoding of names and other strings can be used to allow for some types of typographical variation and data errors. METHODS: A method is described which permits the calculation of a general similarity measure, the n-gram score, without having to reveal the data being compared, albeit at some cost in computation and data communication. This method can be combined with public key cryptography and automatic estimation of linkage model parameters to create an overall system for blindfolded record linkage. RESULTS: The system described offers good protection against misdeeds or security failures by any one party, but remains vulnerable to collusion between or simultaneous compromise of two or more parties involved in the linkage operation. In order to reduce the likelihood of this, the use of last-minute allocation of tasks to substitutable servers is proposed. Proof-of-concept computer programmes written in the Python programming language are provided to illustrate the similarity comparison protocol. CONCLUSION: Although the protocols described in this paper are not unconditionally secure, they do suggest the feasibility, with the aid of modern cryptographic techniques and high speed communication networks, of a general purpose probabilistic record linkage system which permits record linkage studies to be carried out with negligible risk of invasion of personal privacy

Exploratory study of plasma total homocysteine and its relationship to short-term outcome in acute ischaemic stroke in Nigerians

<p>Abstract</p> <p>Background</p> <p>Hyperhomocysteinemia is a potentially modifiable risk factor for stroke, and may have a negative impact on the course of ischaemic stroke. The role of hyperhomocysteinemia as it relates to stroke in Africans is still uncertain. The objective of this study was to determine the prevalence and short-term impact of hyperhomocysteinemia in Nigerians with acute ischaemic stroke. We hypothesized that Hcy levels are significantly higher than in normal controls, worsen stroke severity, and increase short-term case fatality rates following acute ischaemic stroke.</p> <p>Methods</p> <p>The study employed both a case-control and prospective follow-up design to study hospitalized adults with first – ever acute ischaemic stroke presenting within 48 hours of onset. Clinical histories, neurological evaluation (including National Institutes of Health Stroke Scale (NIHSS) scores on admission) were documented. Total plasma Hcy was determined on fasting samples drawn from controls and stroke cases (within 24 hours of hospitalization). Outcome at 4 weeks was assessed in stroke patients using the Glasgow Outcome Scale (GOS).</p> <p>Results</p> <p>We evaluated 155 persons (69 acute ischaemic stroke and 86 healthy controls). The mean age ± SD of the cases was 58.8 ± 9.8 years, comparable to that of controls which was 58.3 ± 9.9 years (T = 0.32; P = 0.75). The mean duration of stroke (SD) prior to hospitalization was 43.5 ± 38.8 hours, and mean admission NIHSS score was 10.1 ± 7.7. Total fasting Hcy in stroke patients was 10.2 ± 4.6 umol/L and did not differ significantly from controls (10.1 ± 3.6 umol/L; P = 0.88). Hyperhomocysteinemia, defined by plasma Hcy levels > 90^thpercentile of controls (>14.2 umol/L in women and >14.6 umol/L in men), was present in 7 (10.1%) stroke cases and 11 (12.8%) controls (odds ratio 0.86, 95% confidence interval 0.31 – 2.39; P > 0.05). In multiple regression analysis admission NIHSS score (but not plasma Hcy) was a significant determinant of 4 week outcome measured by GOS score (P < 0.0001).</p> <p>Conclusion</p> <p>This exploratory study found that homocysteine levels are not significantly elevated in Nigerians with acute ischaemic stroke, and admission Hcy level is not a determinant of short-term (4 week) stroke outcome.</p

Site-Specific Bioconjugation of a Murine Dihydrofolate Reductase Enzyme by Copper(I)-Catalyzed Azide-Alkyne Cycloaddition with Retained Activity

Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is an efficient reaction linking an azido and an alkynyl group in the presence of copper catalyst. Incorporation of a non-natural amino acid (NAA) containing either an azido or an alkynyl group into a protein allows site-specific bioconjugation in mild conditions via CuAAC. Despite its great potential, bioconjugation of an enzyme has been hampered by several issues including low yield, poor solubility of a ligand, and protein structural/functional perturbation by CuAAC components. In the present study, we incorporated an alkyne-bearing NAA into an enzyme, murine dihydrofolate reductase (mDHFR), in high cell density cultivation of Escherichia coli, and performed CuAAC conjugation with fluorescent azide dyes to evaluate enzyme compatibility of various CuAAC conditions comprising combination of commercially available Cu(I)-chelating ligands and reductants. The condensed culture improves the protein yield 19-fold based on the same amount of non-natural amino acid, and the enzyme incubation under the optimized reaction condition did not lead to any activity loss but allowed a fast and high-yield bioconjugation. Using the established conditions, a biotin-azide spacer was efficiently conjugated to mDHFR with retained activity leading to the site-specific immobilization of the biotin-conjugated mDHFR on a streptavidin-coated plate. These results demonstrate that the combination of reactive non-natural amino acid incorporation and the optimized CuAAC can be used to bioconjugate enzymes with retained enzymatic activityope

Cyclic di-GMP is Essential for the Survival of the Lyme Disease Spirochete in Ticks

Cyclic dimeric GMP (c-di-GMP) is a bacterial second messenger that modulates many biological processes. Although its role in bacterial pathogenesis during mammalian infection has been documented, the role of c-di-GMP in a pathogen's life cycle within a vector host is less understood. The enzootic cycle of the Lyme disease pathogen Borrelia burgdorferi involves both a mammalian host and an Ixodes tick vector. The B. burgdorferi genome encodes a single copy of the diguanylate cyclase gene (rrp1), which is responsible for c-di-GMP synthesis. To determine the role of c-di-GMP in the life cycle of B. burgdorferi, an Rrp1-deficient B. burgdorferi strain was generated. The rrp1 mutant remains infectious in the mammalian host but cannot survive in the tick vector. Microarray analyses revealed that expression of a four-gene operon involved in glycerol transport and metabolism, bb0240-bb0243, was significantly downregulated by abrogation of Rrp1. In vitro, the rrp1 mutant is impaired in growth in the media containing glycerol as the carbon source (BSK-glycerol). To determine the contribution of the glycerol metabolic pathway to the rrp1 mutant phenotype, a glp mutant, in which the entire bb0240-bb0243 operon is not expressed, was generated. Similar to the rrp1 mutant, the glp mutant has a growth defect in BSK-glycerol medium. In vivo, the glp mutant is also infectious in mice but has reduced survival in ticks. Constitutive expression of the bb0240-bb0243 operon in the rrp1 mutant fully rescues the growth defect in BSK-glycerol medium and partially restores survival of the rrp1 mutant in ticks. Thus, c-di-GMP appears to govern a catabolic switch in B. burgdorferi and plays a vital role in the tick part of the spirochetal enzootic cycle. This work provides the first evidence that c-di-GMP is essential for a pathogen's survival in its vector host

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Overwintering individuals of the Arctic krill Thysanoessa inermis appear tolerant to short-term exposure to low pH conditions

Areas of the Arctic Ocean are already experiencing seasonal variation in low pH/elevated pCO2 and are predicted to be the most affected by future ocean acidification (OA). Krill play a fundamental ecological role within Arctic ecosystems, serving as a vital link in the transfer of energy from phytoplankton to higher trophic levels. However, little is known of the chemical habitat occupied by Arctic invertebrate species, and of their responses to changes in seawater pH. Therefore, understanding krill’s responses to low pH conditions has important implications for the prediction of how Arctic marine communities may respond to future ocean change. Here, we present natural seawater carbonate chemistry conditions found in the late polar winter (April) in Kongsfjord, Svalbard (79°North) as well as the response of the Arctic krill, Thysanoessa inermis, exposed to a range of low pH conditions. Standard metabolic rate (measured as oxygen consumption) and energy metabolism markers (incl. adenosine triphosphate (ATP) and l-lactate) of T. inermis were examined. We show that after a 7 days experiment with T. inermis, no significant effects of low pH on MO2, ATP and l-lactate were observed. Additionally, we report carbonate chemistry from within Kongsfjord, which showed that the more stratified inner fjord had lower total alkalinity, higher dissolved inorganic carbon, pCO2 and lower pH than the well-mixed outer fjord. Consequently, our results suggest that overwintering individuals of T. inermis may possess sufficient ability to tolerate short-term low pH conditions due to their migratory behaviour, which exposes T. inermis to the naturally varying carbonate chemistry observed within Kongsfjord, potentially allowing T. inermis to tolerate future OA scenarios