114 research outputs found
To Separate or Not to Separate: A Comparative Look at Education in Northern Ireland and the Special Education System in the United States
This paper explores the current debate around the education system in Northern Ireland as part of the peace process in its post-conflict society. It discusses the advantages and disadvantages of integrated and shared education through anecdotes, reflections, observations, and discussions based on experiences in Northern Ireland. This paper also sets out to compare these systems to the debate around full and partial inclusion of students with disabilities in the United States, also discussing the advantages and disadvantages through scholarly articles, observations, and analysis. Finally, it examines the relationship between the two countries and the necessary next steps in terms of policy and action
Structure of the proton-gated urea channel from the gastric pathogen Helicobacter pylori.
Half the world's population is chronically infected with Helicobacter pylori, causing gastritis, gastric ulcers and an increased incidence of gastric adenocarcinoma. Its proton-gated inner-membrane urea channel, HpUreI, is essential for survival in the acidic environment of the stomach. The channel is closed at neutral pH and opens at acidic pH to allow the rapid access of urea to cytoplasmic urease. Urease produces NH(3) and CO(2), neutralizing entering protons and thus buffering the periplasm to a pH of roughly 6.1 even in gastric juice at a pH below 2.0. Here we report the structure of HpUreI, revealing six protomers assembled in a hexameric ring surrounding a central bilayer plug of ordered lipids. Each protomer encloses a channel formed by a twisted bundle of six transmembrane helices. The bundle defines a previously unobserved fold comprising a two-helix hairpin motif repeated three times around the central axis of the channel, without the inverted repeat of mammalian-type urea transporters. Both the channel and the protomer interface contain residues conserved in the AmiS/UreI superfamily, suggesting the preservation of channel architecture and oligomeric state in this superfamily. Predominantly aromatic or aliphatic side chains line the entire channel and define two consecutive constriction sites in the middle of the channel. Mutation of Trp 153 in the cytoplasmic constriction site to Ala or Phe decreases the selectivity for urea in comparison with thiourea, suggesting that solute interaction with Trp 153 contributes specificity. The previously unobserved hexameric channel structure described here provides a new model for the permeation of urea and other small amide solutes in prokaryotes and archaea
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pH-dependent gating mechanism of the Helicobacter pylori urea channel revealed by cryo-EM.
The urea channel of Helicobacter pylori (HpUreI) is an ideal drug target for preventing gastric cancer but incomplete understanding of its gating mechanism has hampered development of inhibitors for the eradication of H. pylori. Here, we present the cryo-EM structures of HpUreI in closed and open conformations, both at a resolution of 2.7 Å. Our hexameric structures of this small membrane protein (~21 kDa/protomer) resolve its periplasmic loops and carboxyl terminus that close and open the channel, and define a gating mechanism that is pH dependent and requires cooperativity between protomers in the hexamer. Gating is further associated with well-resolved changes in the channel-lining residues that modify the shape and length of the urea pore. Site-specific mutations in the periplasmic domain and urea pore identified key residues important for channel function. Drugs blocking the urea pore based on our structures should lead to a new strategy for H. pylori eradication
Terahertz Optomagnetism:Nonlinear THz Excitation of GHz Spin Waves in Antiferromagnetic FeBO3
A nearly single cycle intense terahertz (THz) pulse with peak electric and magnetic fields of 0.5 MV/cm and 0.16 T, respectively, excites both modes of spin resonances in the weak antiferromagnet FeBO3. The high frequency quasiantiferromagnetic mode is excited resonantly and its amplitude scales linearly with the strength of the THz magnetic field, whereas the low frequency quasiferromagnetic mode is excited via a nonlinear mechanism that scales quadratically with the strength of the THz electric field and can be regarded as a THz inverse Cotton-Mouton effect. THz optomagnetism is shown to be more energy efficient than similar effects reported previously for the near-infrared spectral range
Microwave Spin-Pumping from an Antiferromagnet FeBO3
Recently, canted antiferromagnets offer great potential for fundamental
research and applications due to their unique properties. The presence of the
Dzyaloshinskii-Moriya interaction leads to the existence of a weak
ferromagnetic moment at room temperature. We study both theoretically and
experimentally microwave spin pumping by the quasi-ferromagnetic mode from a
canted easy plane antiferromagnet with weak ferromagnetism FeBO3. The
conversion of a microwave signal into the constant voltage is realized using
the inverse spin Hall effect in an iron borate/heavy metal heterostructure. We
use an additional bias magnetic field to selectively tune the resonance
frequency of such a microwave detector over a wide range up to 43.5 GHz with
potential sensitivity near 2.5 microV/W. We confirm the pure spin current
nature by changing polarity of the detected via inverse spin Hall effect
voltage by switching the direction of the bias magnetic field. We believe that
our results will be useful for the development of highly tunable, portable and
sensitive microwave antiferromagnet-based functional devices.Comment: 7 pages, 3 figures, 3 pages supplementary informatio
Education effects on cognitive function in a healthy aged Arab population
Abstract Background-The Minimental State Examination (MMSE) has not been validated in Arabic speaking populations. The Brookdale Cognitive Screening Test (BCST) has been developed for use in low schooling populations. We investigated the influence of gender, education and occupation in a cognitively normal community sample assessed with an Arabic translation of the MMSE and the BCST
Increasing gene dosage greatly enhances recombinant expression of aquaporins in Pichia pastoris
<p>Abstract</p> <p>Background</p> <p>When performing functional and structural studies, large quantities of pure protein are desired. Most membrane proteins are however not abundantly expressed in their native tissues, which in general rules out purification from natural sources. Heterologous expression, especially of eukaryotic membrane proteins, has also proven to be challenging. The development of expression systems in insect cells and yeasts has resulted in an increase in successful overexpression of eukaryotic proteins. High yields of membrane protein from such hosts are however not guaranteed and several, to a large extent unexplored, factors may influence recombinant expression levels. In this report we have used four isoforms of aquaporins to systematically investigate parameters that may affect protein yield when overexpressing membrane proteins in the yeast <it>Pichia pastoris</it>.</p> <p>Results</p> <p>By comparing clones carrying a single gene copy, we show a remarkable variation in recombinant protein expression between isoforms and that the poor expression observed for one of the isoforms could only in part be explained by reduced transcript levels. Furthermore, we show that heterologous expression levels of all four aquaporin isoforms strongly respond to an increase in recombinant gene dosage, independent of the amount of protein expressed from a single gene copy. We also demonstrate that the increased expression does not appear to compromise the protein folding and the membrane localisation.</p> <p>Conclusions</p> <p>We report a convenient and robust method based on qPCR to determine recombinant gene dosage. The method is generic for all constructs based on the pPICZ vectors and offers an inexpensive, quick and reliable means of characterising recombinant <it>P. pastoris </it>clones. By using this method we show that: (1) heterologous expression of all aquaporins investigated respond strongly to an increase in recombinant gene dosage (2) expression from a single recombinant gene copy varies in an isoform dependent manner (3) the poor expression observed for AtSIP1;1 is mainly caused by posttranscriptional limitations. The protein folding and membrane localisation seems to be unaffected by increased expression levels. Thus a screen for elevated gene dosage can routinely be performed for identification of <it>P. pastoris </it>clones with high expression levels of aquaporins and other classes of membrane proteins.</p
EFFECT OF THE GAS MEDIA AND TEMPERATURE REGIMES OF ANNEALING ON THE PHASE COMPOSITION OF IRON BORATE FeBO3
Iron borate FeBO3 crystals are annealed in neutral, oxidizing, and reducing gas media on a specially designed setup. The effect of the chemical medium and annealing modes on the surface morphology and phase composition of the samples is established.Исследования выполнены при финансовой поддержке РФФИ, проект № 19-29-12016-мк, в части разработки экспериментальной установки и получения кристаллических образцов. Рентгеновские и электронно-микроскопические измерения проведены при под-держке Министерства науки и высшего образования РФ в рамках выполнения работ по Государственному заданию ФНИЦ «Кристаллография и фотоника» с использованием оборудования ЦКП (проект RFMEFI62119X0035)
HYPERFINE INTERACTIONS IN IRON BORATE FeBO3
For the FeBO3 single crystal, the values of isomer shift, quadrupole constant and magnetic hyperfine field were determined for over a wide temperature range.Исследования выполнены при финансовой поддержке РФФИ, проект № 19-29-12016-мк, в части мёссбауэровских исследований и теоретического анализа. Рентгеновские измерения проведены при поддержке Министерства науки и высшего образования РФ в рамках выполнения работ по Государственному заданию ФНИЦ «Кристаллография и фотоника» с использованием оборудования ЦКП (проект RFMEFI62119X0035)
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.
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