The large ribosomal subunit catalyzes peptide bond formation and binds initiation, termination, and elongation factors. We have determined the crystal structure of the large ribosomal subunit from ...Haloarcula marismortui at 2.4 angstrom resolution, and it includes 2833 of the subunit's 3045 nucleotides and 27 of its 31 proteins. The domains of its RNAs all have irregular shapes and fit together in the ribosome like the pieces of a three-dimensional jigsaw puzzle to form a large, monolithic structure. Proteins are abundant everywhere on its surface except in the active site where peptide bond formation occurs and where it contacts the small subunit. Most of the proteins stabilize the structure by interacting with several RNA domains, often using idiosyncratically folded extensions that reach into the subunit's interior.
Cyclized‐polyacrylonitrile (cyclized‐PAN) is used as a conformal coating on nano‐Si for highly reversible anodes. Cyclization of PAN proceeds by limiting the pyrolysis to 300 °C such that the ...cyclized‐PAN maintains its polymeric properties while also providing sp2 π bonding for good electronic conductivity. Cyclized‐PAN is thus a conjugated polymer with good mechanical resiliency to accommodate Si's volumetric expansion and also good mixed conductivity.
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The history of pharmacotherapy of mental illness can be divided into three periods.
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Introduction of morphine, potassium bromide, chloral hydrate, hyoscine, paraldehyde, etc., during the second ...half of the 19th century (first period), led to the replacement of physical restraint by pharmacological means in behavior control.
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Introduction of nicotinic acid, penicillin, thiamine, etc., during the first half of the 20th century (second period), led to significant changes in the diagnostic distribution of psychiatric patients; psychoses due to cerebral pellagra, and dementia due to syphilitic general paralysis virtually disappeared from psychiatric hospitals, and the prevalence of dysmnesias markedly decreased.
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Treatment with therapeutically effective drugs of mania, schizophrenia, depression, bipolar disorder, generalized anxiety disorder, panic disorder, obsessive compulsive disorder, Alzheimer's disease, etc., during the second half of the 20th century (third period), brought to attention the heterogeneity of the populations within the diagnostic categories of schizophrenia and depression.
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Introduction of the first set of psychotropics and the spectrophotofluorimeter during the 1950s triggered the development of neuropsychopharmacology.
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Introduction of genetic technology for the separation of receptor subtypes in the 1980s opened the path for the “tailoring” of psychotropic drugs by the dawn of the 21st century, to receptor affinities.
Association studies have greatly refined the understanding of how variation within the human leukocyte antigen (HLA) genes influences risk of multiple sclerosis. However, the extent to which major ...effects are modulated by interactions is poorly characterized. We analyzed high-density SNP data on 17,465 cases and 30,385 controls from 11 cohorts of European ancestry, in combination with imputation of classical HLA alleles, to build a high-resolution map of HLA genetic risk and assess the evidence for interactions involving classical HLA alleles. Among new and previously identified class II risk alleles (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving pairs of class II alleles: HLA-DQA1*01:01-HLA-DRB1*15:01 and HLA-DQB1*03:01-HLA-DQB1*03:02. We find no evidence for interactions between classical HLA alleles and non-HLA risk-associated variants and estimate a minimal effect of polygenic epistasis in modulating major risk alleles.
We present an analytical method for the calculation of electromagnetic torque in surface permanent-magnet (PM) motors. Our method uses conformal mapping to calculate the electromagnetic torque by ...integrating the Maxwell stress tensor inside the air gap. It uses the radial and tangential components of the flux density in the slotted air-gap produced by the currents flowing in the three-phase armature winding. We demonstrate our analytical solution on a 7-kW four-pole surface PM motor and compare the results with finite-element solutions. We present the results for various angular spans of permanent magnets and various sizes of the slot opening to confirm the validity of the analytical approach.
We have investigated the possibility to use swift heavy ion irradiation for nano-structuring supported and freestanding ultra-thin MoS2 samples. Our comprehensive study of the ion-induced ...morphological changes in various MoS2 samples shows that depending on the irradiation parameters a multitude of extended defects can be fabricated. These range from chains of nano-hillocks in bulk-like MoS2, and foldings in single and bilayer MoS2, to unique nano-incisions in supported and freestanding single layers of MoS2. Our data reveals that the primary mechanism responsible for the incisions in the ultrathin supported samples is the indirect heating by the SiO2 substrate. We thus conclude that an energy of less than 2 keV per nm track length is sufficient to fabricate nano-incisions in MoS2 which is compatible with the use of the smallest accelerators.
We have calculated at 5.0 A resolution an electron-density map of the large 50S ribosomal subunit from the bacterium Haloarcula marismortui by using phases derived from four heavy-atom derivatives, ...intercrystal density averaging and density-modification procedures. More than 300 base pairs of A-form RNA duplex have been fitted into this map, as have regions of non-A-form duplex, single-stranded segments and tetraloops. The long rods of RNA crisscrossing the subunit arise from the stacking of short, separate double helices, not all of which are A-form, and in many places proteins crosslink two or more of these rods. The polypeptide exit channel was marked by tungsten cluster compounds bound in one heavy-atom-derivatized crystal. We have determined the structure of the translation-factor-binding centre by fitting the crystal structures of the ribosomal proteins L6, L11 and L14, the sarcin-ricin loop RNA, and the RNA sequence that binds L11 into the electron density. We can position either elongation factor G or elongation factor Tu complexed with an aminoacylated transfer RNA and GTP onto the factor-binding centre in a manner that is consistent with results from biochemical and electron microscopy studies.
We have calculated at 5.0 A resolution an electron-density map of the large 50S ribosomal subunit from the bacterium Haloarcula marismortui by using phases derived from four heavy-atom derivatives, ...intercrystal density averaging and density-modification procedures. More than 300 base pairs of A-form RNA duplex have been fitted into this map, as have regions of non-A-form duplex, single-stranded segments and tetraloops. The long rods of RNA crisscrossing the subunit arise from the stacking of short, separate double helices, not all of which are A-form, and in many places proteins crosslink two or more of these rods. The polypeptide exit channel was marked by tungsten cluster compounds bound in one heavy-atom-derivatized crystal. We have determined the structure of the translation-factor-binding centre by fitting the crystal structures of the ribosomal proteins L6, L11 and L14, the sarcin-ricin loop RNA, and the RNA sequence that binds L11 into the electron density. We can position either elongation factor G or elongation factor Tu complexed with an aminoacylated transfer RNA and GTP onto the factor-binding centre in a manner that is consistent with results from biochemical and electron microscopy studies.
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