Cryogenic magnetocaloric effect in the Fe17 molecular nanomagnet

Trabajo presentado al "The 23rd IIR International Congress of Refrigeration" celebrado del 21 al 26 de Agosto del 2011 en Praga.-- Dedicated to Alfred Werner on the 100th Anniversary of his Nobel prize in Chemistry in 1913.We study the magnetothermal properties of magnetically isotropic high-spin molecular nanomagnets containing 17 Fe3+ ions per molecule linked via oxide and hydroxide ions, packed in a crystallographic cubic symmetry. Low-temperature magnetization and heat capacity experiments reveal that each molecular unit carries a net spin ground state as large as S = 35/2 and a magnetic anisotropy as small as D = −0.023 K, while no magnetic order, purely driven by dipolar interactions, is to be expected down to very-low temperatures. These characteristics suggest that the Fe17 molecular nanomagnet can potentially be employed as a sub-Kelvin magnetic refrigerant.This work has been partially supported by Spanish MINECO through grants MAT2009-13977-C03 and PIE201060I012, the EPSRC and The Leverhulme Trust (UK).Peer Reviewe

Spectroscopic and inclusion properties of G-series chemical warfare agents and their simulants: a DFT study

A computational protocol to predict the infrared spectra of chemical warfare agents (CWAs) tabun (GA), sarin (GB), soman (GD) and cyclosarin (GF) has been developed. Sarin was used to benchmark the method through gas phase simulations. DFT calculations using the EDF2 functional and diffuse 6-311++G** basis set was found to give the closest match to experimental infrared spectra. Using the same functional the 6-31G (2df, 2p) basis set was found to be superior when hydrated sarin was modelled. GA, GB, GD and GF, together with 11 commonly used simulants, were modelled in the gas and hydrated states. Complexes of GB and a number of CWA mimics with α-cyclodextrin were modelled to give insight into their different modes of inclusion

Experimental and computational study of the inclusion complexes of b-cyclodextrin with the chemical warfare agent soman (GD) and commonly used simulants

The hydrophobically driven inclusion complexation of the Chemical Warfare Agent (CWA) pinacolylmethylphosphonofluoridate (soman, or GD) by b-cyclodextrin (b-CD) is studied both experimentally and computationally. Semiempirical modelling (PM6) adds further insight to the understanding of the CD–GD complex and the preferential binding of P(+) isomers over P(-). Comparison of the CD–GD complex to those formed by b-CD with commonly used trialkyl phosphate and dialkyl methylphosphonate simulants furnishes preliminary supramolecular agent–simulant correlation data. Such comparison studies will haveutility in the design of new CWA-responsive materials

Hexahalorhenate (iv) salts of metal oxazolidine nitroxides

Eight coordination compounds of formulae [FeII(L•)2][ReIVCl6] (1a), [FeII(L•)2][ReIVBr6] (1b), [CoII(L•)2][ReIVCl6]·CH3CN (2a), [CoII(L•)2][ReIVBr6] (2b), [NiII(L•)(CH3CN)3][ReIVCl6]·CH3CN (3a), [NiII(L•)(CH3CN)3][ReIVBr6]·3CH3CN (3b), [CuII(L•)2][ReIVCl6] (4a)and [CuII(L•)2][ReIVBr6] (4b), where L• is the aminoxyl radical chelating ligand, 4,4-dimethyl-2,2-di(2-pyridyl)oxazolidine-N- oxide, have been synthesised. Structural and magnetic studies reveal metal-radical intramolecular antiferromagnetic interactions in the [MII(L•)2]2+ cations in the iron, cobalt and copper based compounds (1a, 1b, 2a, 2b, 4a and 4b) with the central metal ion low-spin in the case of Fe (1a and 1b) and a gradual, cobalt based, spin-crossover transition present in 2a and 2b. The nickel based compounds, 3a and 3b, were analysed in the dried form (3a(dried) and 3b(dried)) and directly in acetonitrile (3a(solvated) and 3b(solvated)). Microanalysis and IR spectroscopy on 3a(dried) and 3b(dried) suggests the dried samples are best formulated as [NiII(L•)(H2O)3][ReIVX6], where X = Cl (3a(dried)) and Br (3b(dried)). All forms for 3a and 3b exhibit cationic metal-radical ferromagnetic interactions resulting in S = 3/2 ground states. In addition, 3a(dried) exhibits spin-canting behaviour with an ordering temperature of 2.7 K, an open hysteresis loop with a coercive field Hc, = 580 Oe, and a remanent magnetisation Mr = 0.21 μB, resulting in a canting angle of ~1.8°. In contrast 3b(dried) shows no spin-canting behaviour; a maximum in χM vs. T at T = 3 K suggesting long-range antiferromagnetic order. 3a(solvated) and 3b(solvated) show no indication of long-range magnetic ordering, unlike 4a and 4b where anomalies are evident in the low-temperature magnetic susceptibility measurements

High-field ground-state level crossing and magnetic susceptibility of an {Fe-8}-cubane cluster

The differential susceptibility, dM/dH, of an Fe8-cubane cluster has been measured for magnetic fields up to 54 T at 1.3 and 4.2 K using a pulsed-field technique. The data feature a single strong peak at 42 ± 1 T, corresponding to a ground state level crossing at that field, in excellent agreement with the predicted value, 41 ± 1 T, obtained using a Heisenberg model of the cluster. The theoretical model also accurately accounts for detailed features of the temperature and field dependence of the width and height of the observed peak

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

The use of the TCNQF₄^2-dianion in the spontaneous redox formation of [Fe^III(L^-)₂][TCNQF₄•-]

The reaction of [FeII(L •)2](BF4)2 with Li2TCNQF4 results in the formation of [FeIII(L-)2][TCNQF4•-] (1) where L• is the radical ligand, 4,4-dimethyl-2,2-di(2-pyridyl)oxazolidine-N-oxide and TCNQF4 is 2,3,5,6-Tetrafluoro-7,7,8,8-tetracyano-quinodimethane. This has been characterised by x-ray diffraction, Raman and Fourier-transform infra-red (FTIR) spectroscopy, variable temperature magnetic susceptibility, Mössbauer spectroscopy and electrochemistry. X-ray diffraction studies, magnetic susceptibility measurements and Raman and FTIR spectroscopy suggest the presence of low-spin FeIII ion, the anionic form (L-­) of the ligand and the anionic radical form of TCNQF4; TCNQF4•-. Li2TCNQF4 reduces the [FeII(L•)2]2+ dication which undergoes a reductively induced oxidation to form the [FeIII(L-)2]+ monocation resulting in the formation of [FeIII(L-)2][TCNQF4•-] (1), the electrochemistry of which revealed four well-separated, diffusion controlled, one-electron, reversible processes. Mössbauer spectroscopy and electrochemical measurements suggest the presence of a minor second species, likely to be [FeII(L•)2][TCNQF42-]

National Outbreak of Salmonella Serotype Saintpaul Infections: Importance of Texas Restaurant Investigations in Implicating Jalapeño Peppers

BACKGROUND: In May 2008, PulseNet detected a multistate outbreak of Salmonella enterica serotype Saintpaul infections. Initial investigations identified an epidemiologic association between illness and consumption of raw tomatoes, yet cases continued. In mid-June, we investigated two clusters of outbreak strain infections in Texas among patrons of Restaurant A and two establishments of Restaurant Chain B to determine the outbreak's source. METHODOLOGY/PRINCIPAL FINDINGS: We conducted independent case-control studies of Restaurant A and B patrons. Patients were matched to well controls by meal date. We conducted restaurant environmental investigations and traced the origin of implicated products. Forty-seven case-patients and 40 controls were enrolled in the Restaurant A study. Thirty case-patients and 31 controls were enrolled in the Restaurant Chain B study. In both studies, illness was independently associated with only one menu item, fresh salsa (Restaurant A: matched odds ratio [mOR], 37; 95% confidence interval [CI], 7.2-386; Restaurant B: mOR, 13; 95% CI 1.3-infinity). The only ingredient in common between the two salsas was raw jalapeño peppers. Cultures of jalapeño peppers collected from an importer that supplied Restaurant Chain B and serrano peppers and irrigation water from a Mexican farm that supplied that importer with jalapeño and serrano peppers grew the outbreak strain. CONCLUSIONS/SIGNIFICANCE: Jalapeño peppers, contaminated before arrival at the restaurants and served in uncooked fresh salsas, were the source of these infections. Our investigations, critical in understanding the broader multistate outbreak, exemplify an effective approach to investigating large foodborne outbreaks. Additional measures are needed to reduce produce contamination

Common variation in the miR-659 binding-site of GRN is a major risk factor for TDP43-positive frontotemporal dementia

Loss-of-function mutations in progranulin (GRN) cause ubiquitin- and TAR DNA-binding protein 43 (TDP-43)-positive frontotemporal dementia (FTLD-U), a progressive neurodegenerative disease affecting ∼10% of early-onset dementia patients. Here we expand the role of GRN in FTLD-U and demonstrate that a common genetic variant (rs5848), located in the 3′-untranslated region (UTR) of GRN in a binding-site for miR-659, is a major susceptibility factor for FTLD-U. In a series of pathologically confirmed FTLD-U patients without GRN mutations, we show that carriers homozygous for the T-allele of rs5848 have a 3.2-fold increased risk to develop FTLD-U compared with homozygous C-allele carriers (95% CI: 1.50–6.73). We further demonstrate that miR-659 can regulate GRN expression in vitro, with miR-659 binding more efficiently to the high risk T-allele of rs5848 resulting in augmented translational inhibition of GRN. A significant reduction in GRN protein was observed in homozygous T-allele carriers in vivo, through biochemical and immunohistochemical methods, mimicking the effect of heterozygous loss-of-function GRN mutations. In support of these findings, the neuropathology of homozygous rs5848 T-allele carriers frequently resembled the pathological FTLD-U subtype of GRN mutation carriers. We suggest that the expression of GRN is regulated by miRNAs and that common genetic variability in a miRNA binding-site can significantly increase the risk for FTLD-U. Translational regulation by miRNAs may represent a common mechanism underlying complex neurodegenerative disorders

An evaluation of 9-1-1 calls to assess the effectiveness of dispatch-assisted cardiopulmonary resuscitation (CPR) instructions: design and methodology

<p>Abstract</p> <p>Background</p> <p>Cardiac arrest is the leading cause of mortality in Canada, and the overall survival rate for out-of-hospital cardiac arrest rarely exceeds 5%. Bystander cardiopulmonary resuscitation (CPR) has been shown to increase survival for cardiac arrest victims. However, bystander CPR rates remain low in Canada, rarely exceeding 15%, despite various attempts to improve them. Dispatch-assisted CPR instructions have the potential to improve rates of bystander CPR and many Canadian urban communities now offer instructions to callers reporting a victim in cardiac arrest. Dispatch-assisted CPR instructions are recommended by the International Guidelines on Emergency Cardiovascular Care, but their ability to improve cardiac arrest survival remains unclear.</p> <p>Methods/Design</p> <p>The overall goal of this study is to better understand the factors leading to successful dispatch-assisted CPR instructions and to ultimately save the lives of more cardiac arrest patients. The study will utilize a before-after, prospective cohort design to specifically: 1) Determine the ability of 9-1-1 dispatchers to correctly diagnose cardiac arrest; 2) Quantify the frequency and impact of perceived agonal breathing on cardiac arrest diagnosis; 3) Measure the frequency with which dispatch-assisted CPR instructions can be successfully completed; and 4) Measure the impact of dispatch-assisted CPR instructions on bystander CPR and survival rates.</p> <p>The study will be conducted in 19 urban communities in Ontario, Canada. All 9-1-1 calls occurring in the study communities reporting out-of-hospital cardiac arrest in victims 16 years of age or older for which resuscitation was attempted will be eligible. Information will be obtained from 9-1-1 call recordings, paramedic patient care reports, base hospital records, fire medical records and hospital medical records. Victim, caller and system characteristics will be measured in the study communities before the introduction of dispatch-assisted CPR instructions (before group), during the introduction (run-in phase), and following the introduction (after group).</p> <p>Discussion</p> <p>The study will obtain information essential to the development of clinical trials that will test a variety of educational approaches and delivery methods for telephone cardiopulmonary resuscitation instructions. This will be the first study in the world to clearly quantify the impact of dispatch-assisted CPR instructions on survival to hospital discharge for out-of-hospital cardiac arrest victims.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00664443</p