Charge-Transfer Forces in the Self-Assembly of Heteromolecular Reactive Solids: Successful Design of Unique (Single-Crystal-to-Single-Crystal) Diels−Alder Cycloadditions

Electron donor/acceptor (EDA) interactions are found to be a versatile methodology for the engineering of reactive heteromolecular crystals. In this way, a series of the charge-transfer π-complexes between bis(alkylimino)-1,4-dithiin acceptors and anthracene donors are shown to form heteromolecular (1:1) crystalline solids that spontaneously undergo stereoselective [2 + 4] Diels−Alder cycloadditions. The flexible nature of the 1,4-dithiin moiety allows this homogeneous topochemical transformation to proceed with minimal distortion of the crystal lattice. As a result, a unique (single) crystal phase of the Diels−Alder adduct can be produced anti-thermodynamically with a molecular arrangement very different from that in solvent-grown crystals. Such a topochemical reaction between bis(methylimino)-1,4-dithiin and anthracene proceeds thermally and homogeneously up to very high conversions without disintegration of the single crystal. This ideal case of the mono-phase topochemical conversion can be continuously monitored structurally (X-ray crystallography) and kinetically (NMR spectroscopy) throughout the entire range of the crystalline transformation. The resultant “artificial” crystal of the Diels−Alder adduct is surprisingly stable despite its different symmetry and packing mode compared to the naturally grown (thermodynamic) crystal

Diels−Alder Topochemistry via Charge-Transfer Crystals: Novel (Thermal) Single-Crystal-to-Single-Crystal Transformations

The solid-state [4+2] cycloaddition of anthracene to bis(N-ethylimino)-1,4-dithiin occurs via a unique single-phase topochemical reaction in the intermolecular (1:1) charge-transfer crystal. The thermal heteromolecular solid-state condensation involves the entire crystal, and this rare crystalline event follows topochemical control during the entire cycloaddition. As a result, a new crystalline modification of the Diels−Alder product is formed with a crystal-packing similar to that of the starting charge-transfer crystal but very different from that of the (thermodynamically favored) product modification obtained from solution-phase crystallization. Such a single-phase transformation is readily monitored by X-ray crystallography at various conversion stages, and the temporal changes in crystallographic parameters are correlated with temperature-dependent (solid-state) kinetic data that are obtained by 1H NMR spectroscopy at various reaction times. Thus, an acceleration of the solid-state reaction over time is found which results from a progressive lowering of the activation barrier for cycloaddition in a single crystal as it slowly and homogeneously converts from the reactant to the product lattice

Comparison of complications of spinal and general anesthasia in percutaneous kidney stone removal

While the complications of spinal anesthesia are much less than general anesthesia, percutaneous nephrolithotomy (PCNL) is still performed under general anesthesia in most centers. Therefore, in this study spinal anesthesia is compared with general anesthesia in patients undergoing PCNL. This research was a double-blind clinical trial study which was conducted on 130 patients with inclusion criteria. Patients were nonrandomly assigned into two general anesthesia (n=65) and spinal anesthesia (n=65) groups and underwent PCNL surgery.In group A, patients were given intravenously midazolam (2 mg), fentanyl (100 μg), atracurium (0.5 mg/kg), propofol (2 mg/kg) and morphine (10 mg) and then were incubated. In group B, Marcaine 0.5% (15 mg) was injected into the L3-L4 or L4-L5 lumbar spinal space in a sitting position. Patient’s blood pressure was measured and recorded at various times and in recovery as well as in the surgery room. Intra-operative bleeding, pain in the surgery area, nausea and vomiting, shortness of breath and sore throat were recorded for the two groups in the ward and during hospitalization.Changes of blood pressure were the same in both groups. In the general anesthesia group, intra-operative bleeding, pain at the site of the surgery, nausea and vomiting, shortness of breath and sore throat and duration of hospitalization were significantly higher. Changes in other tests were equal in both groups. Spinal anesthesia might be a safer method than general anesthesia for PCNL surgery.Keywords: Complication, Spinal Anesthesia, General Anesthesia, Kidney Stone Removal, Percutaneou

Charge Delocalization in Self-Assembled Mixed-Valence Aromatic Cation Radicals

The spontaneous assembly of aromatic cation radicals (D+•) with their neutral counterpart (D) affords dimer cation radicals (D2+•). The intermolecular dimeric cation radicals are readily characterized by the appearance of an intervalence charge-resonance transition in the NIR region of their electronic spectra and by ESR spectroscopy. The X-ray crystal structure analysis and DFT calculations of a representative dimer cation radical (i.e., the octamethylbiphenylene dimer cation radical) have established that a hole (or single positive charge) is completely delocalized over both aromatic moieties. The energetics and the geometrical considerations for the formation of dimer cation radicals is deliberated with the aid of a series of cyclophane-like bichromophoric donors with drastically varied interplanar angles between the cofacially arranged aryl moieties. X-ray crystallography of a number of mixed-valence cation radicals derived from monochromophoric benzenoid donors established that they generally assemble in 1D stacks in the solid state. However, the use of polychromophoric intervalence cation radicals, where a single charge is effectively delocalized among all of the chromophores, can lead to higher-order assemblies with potential applications in long-range charge transport. As a proof of concept, we show that a single charge in the cation radical of a triptycene derivative is evenly distributed on all three benzenoid rings and this triptycene cation radical forms a 2D electronically coupled assembly, as established by X-ray crystallography

Myelin Basic Protein as a Novel Genetic Risk Factor in Rheumatoid Arthritis—A Genome-Wide Study Combined with Immunological Analyses

Rheumatoid arthritis (RA) is a major cause of adult chronic inflammatory arthritis and a typical complex trait. Although several genetic determinants have been identified, they account for only a part of the genetic susceptibility. We conducted a genome-wide association study of RA in Japanese using 225,079 SNPs genotyped in 990 cases and 1,236 controls from two independent collections (658 cases and 934 controls in collection1; 332 cases and 302 controls in collection2), followed by replication studies in two additional collections (874 cases and 855 controls in collection3; 1,264 cases and 948 controls in collection4). SNPs showing p<0.005 in the first two collections and p<10−4 by meta-analysis were further genotyped in the latter two collections. A novel risk variant, rs2000811, in intron2 of the myelin basic protein (MBP) at chromosome 18q23 showed strong association with RA (p = 2.7×10−8, OR 1.23, 95% CI: 1.14–1.32). The transcription of MBP was significantly elevated with the risk allele compared to the alternative allele (p<0.001). We also established by immunohistochemistry that MBP was expressed in the synovial lining layer of RA patients, the main target of inflammation in the disease. Circulating autoantibody against MBP derived from human brain was quantified by ELISA between patients with RA, other connective tissue diseases and healthy controls. As a result, the titer of anti-MBP antibody was markedly higher in plasma of RA patients compared to healthy controls (p<0.001) and patients with other connective tissue disorders (p<0.001). ELISA experiment using citrullinated recombinant MBP revealed that a large fraction of anti-MBP antibody in RA patients recognized citrullinated MBP. This is the first report of a genetic study in RA implicating MBP as a potential autoantigen and its involvement in pathogenesis of the disease

35 años de análisis de isótopos estables en la arqueología Argentina: conceptos, fundamentos, metodología y aplicaciones

El objetivo de este trabajo es celebrar más de tres décadas de la integración de los análisis de isótopos estables en investigaciones arqueológicas en nuestro país. Se presenta una síntesis sobre los conceptos,fundamentos teóricos y metodológicos y las aplicaciones, principalmente en tres grandes temas: paleodieta, paleomovilidad y paleoambiente. A su vez, brindamos ejemplos de abordajes isotópicos sobre problemáticas de paleodietas en sociedades cazadoras recolectoras y agricultoras; movilidad de grupos humanos; estrategias de pastoreo; preparación y cocción de alimentos; estudios paleoambientales y paleoclimáticos. Este compendio puede resultar una referencia útil para estudiantes e investigadores que decidan adentrarse en este campo de investigación. Los casos mencionados no agotan el estado de la cuestión, ni abarcan todas las regiones donde fueron desarrollados estos estudios, sino que el propósito es mostrar la diversidad temática y el modo en que los isótopos estables permiten ampliar el conocimiento sobre las sociedades en el pasado.The main goal of this work is to celebrate more than three decades of the application of stable isotope analyses in Argentinian archaeology. We present a synthesis of the concepts, theoretical and methodological aspects and applications covering three main topics: paleodiet, paleomobility and paleoenvironment. At the same time, we provide examples of isotopic approaches to study problems such as paleodiets in hunter-gatherer and agricultural societies, human mobility, herding strategies, food preparation and cooking, and paleoenvironmental and paleoclimatic studies. This compendium will be a useful reference for students and researchers inclined to enter this field of research. However, the cases mentioned here do not represent the state of art nor do they cover all the Argentinian regions where these studies were carried out, but rather show the thematic diversity and the way in which stable isotope analyses allow to broaden our knowledge about societies in the past.Introducción - Conceptos básicos, fundamentación y notación de los análisis de isótopos estables - Espectrometría de masas - Relaciones isotópicas mayormente utilizadas en arqueología -- Isótopos estables del carbono -- Isótopos estables del nitrógeno -- Isótopos estables del oxígeno e hidrógeno -- Otras relaciones isotópicas de interés: azufre y estroncio - Tejidos y materiales -- Tejidos biológicos -- Residuos orgánicos -- Carbonatos biogénicos -- Sedimentos - Conservación, contaminación y diagénesis -- Fracción orgánica o colágeno -- Fracción Mineral o Bioapatita - Discriminación y fraccionamiento isotópico - Interpretación paleodietaria y ecología isotópica - Abordajes isotópicos de problemáticas en arqueología argentina - Consideraciones finales y perspectivas futura

Genetic association of zinc transporter 8 (ZnT8) autoantibodies in type 1 diabetes cases

Autoantibodies to zinc transporter 8 (ZnT8A) are associated with risk of type 1 diabetes. Apart from the SLC30A8 gene itself, little is known about the genetic basis of ZnT8A. We hypothesise that other loci in addition to SLC30A8 are associated with ZnT8A. The levels of ZnT8A were measured in 2,239 British type 1 diabetic individuals diagnosed before age 17 years, with a median duration of diabetes of 4 years. Cases were tested at over 775,000 loci genome wide (including 53 type 1 diabetes associated regions) for association with positivity for ZnT8A. ZnT8A were also measured in an independent dataset of 855 family members with type 1 diabetes. Only FCRL3 on chromosome 1q23.1 and the HLA class I region were associated with positivity for ZnT8A. rs7522061T &gt; C was the most associated single nucleotide polymorphism (SNP) in the FCRL3 region (p = 1.13 x 10(-16)). The association was confirmed in the family dataset (p a parts per thousand currency signaEuro parts per thousand 9.20 x 10(-4)). rs9258750A &gt; G was the most associated variant in the HLA region (p = 2.06 x 10(-9) and p = 0.0014 in family cases). The presence of ZnT8A was not associated with HLA-DRB1, HLA-DQB1, HLA-A, HLA-B or HLA-C (p &gt; 0.05). Unexpectedly, the two loci associated with the presence of ZnT8A did not alter risk of having type 1 diabetes, and the 53 type 1 diabetes risk loci did not influence positivity for ZnT8A, despite them being disease specific. ZnT8A are not primary pathogenic factors in type 1 diabetes. Nevertheless, ZnT8A testing in combination with other autoantibodies facilitates disease prediction, despite the biomarker not being under the same genetic control as the disease

Mycobacterium tuberculosis complex drug resistance pattern and identification of species causing tuberculosis in the West and Centre regions of Cameroon

<p>Abstract</p> <p>Background</p> <p>Data on the levels of resistance of <it>Mycobacterium tuberculosis </it>complex (MTBC) strains to first line anti-tuberculosis drugs in Cameroon, and on the species of MTBC circulating in the country are obsolete. The picture about 10 years after the last studies, and 6 years after the re-organisation of the National Tuberculosis (TB) Control Programme (NTBCP) is not known.</p> <p>Methods</p> <p>The study was conducted from February to July 2009 in the West and Centre regions of Cameroon. A total of 756 suspected patients were studied. MTBC species were detected by the standard Ziehl-Neelsen staining method. Bacterial susceptibility to the first line drugs [isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and streptomycin (SM)] were performed on cultures using the indirect proportion method. MTBC species were identified by standard biochemical and culture methods.</p> <p>Results</p> <p>Of the 756 suspected patients, 154 (20.37%) were positive by smear microscopy. Of these, 20.77% were HIV patients. The growth of <it>Mycobacterium </it>was observed with the sputa from 149 (96.75%) subjects. All the isolates were identified as either <it>M. tuberculosis </it>or <it>M. africanum</it>. Among these, 16 (10.73%) were resistant to at least one drug (13.3% for the West region and 8.1% for the Centre). The initial resistance rates were 7.35% for the Centre region and 11.29% for the West region, while the acquired resistance rates were 16.66% (1/6) for the Centre region and 23.07% (3/13) for the West. Within the two regions, the highest total resistance to one drug was obtained with INH and SM (2.68% each). Multidrug-resistance (MDR) was observed only in the West region at a rate of 6.67%. No resistance was recorded for EMB.</p> <p>Conclusions</p> <p><it>M. tuberculosis </it>and <it>M. africanum </it>remain the MTBC species causing pulmonary TB in the West and Centre regions of Cameroon. Following the re-organisation of the NTBCP, resistance to all first line anti-TB drugs has declined significantly (<it>p </it>< 0.05 for West; and <it>p </it>< 0.01 for Centre) in comparison to previous studies. However, the general rates of anti-TB drug resistance remain high in the country, underscoring the need for greater enforcement of control strategies.</p