Charge density mismatch synthesis of MEI- and BPH-type zeolites in the TEA+–TMA+–Li+–Sr2+ mixed-structure-directing agent system

Nanocrystalline MEI- and BPH-type zeolites, denoted as PST-11 and PST-12, respectively, have been synthesized using both tetraethylammonium and tetramethylammonium ions, the two simplest alkyl-ammonium species, in the presence of Li+ and Sr2+. PST-12 formation is the first example of a combination of forced and multiple cooperative structure-directions in the charge density mismatch synthesis of zeolites.open1166sciescopu

Molecular Mechanism of Action of Antimalarial Benzoisothiazolones: Species-Selective Inhibitors of the Plasmodium spp. MEP Pathway enzyme, IspD

The methylerythritol phosphate (MEP) pathway is an essential metabolic pathway found in malaria parasites, but absent in mammals, making it a highly attractive target for the discovery of novel and selective antimalarial therapies. Using high-throughput screening, we have identified 2-phenyl benzo[d]isothiazol-3(2H)-ones as species-selective inhibitors of Plasmodium spp. 2-C-methyl-D-erythritol-4-phosphate cytidyltransferase (IspD), the third catalytic enzyme of the MEP pathway. 2-Phenyl benzo[d]isothiazol-3(2H)-ones display nanomolar inhibitory activity against P. falciparum and P. vivax IspD and prevent the growth of P. falciparum in culture, with EC50 values below 400 nM. In silico modeling, along with enzymatic, genetic and crystallographic studies, have established a mechanism-of-action involving initial non-covalent recognition of inhibitors at the IspD binding site, followed by disulfide bond formation through attack of an active site cysteine residue on the benzo[d]isothiazol-3(2H)-one core. The species-selective inhibitory activity of these small molecules against Plasmodium spp. IspD and cultured parasites suggests they have potential as lead compounds in the pursuit of novel drugs to treat malaria

Selective scattering between Floquet-Bloch and Volkov states in a topological insulator

The coherent optical manipulation of solids is emerging as a promising way to engineer novel quantum states of matter. The strong time periodic potential of intense laser light can be used to generate hybrid photon-electron states. Interaction of light with Bloch states leads to Floquet-Bloch states which are essential in realizing new photo-induced quantum phases. Similarly, dressing of free electron states near the surface of a solid generates Volkov states which are used to study non-linear optics in atoms and semiconductors. The interaction of these two dynamic states with each other remains an open experimental problem. Here we use Time and Angle Resolved Photoemission Spectroscopy (Tr-ARPES) to selectively study the transition between these two states on the surface of the topological insulator Bi2Se3. We find that the coupling between the two strongly depends on the electron momentum, providing a route to enhance or inhibit it. Moreover, by controlling the light polarization we can negate Volkov states in order to generate pure Floquet-Bloch states. This work establishes a systematic path for the coherent manipulation of solids via light-matter interaction.Comment: 21 pages, 6 figures, final version to appear in Nature Physic

Structure of the ArgRS-GlnRS-AIMP1 complex and its implications for mammalian translation

In higher eukaryotes, one of the two arginyl-tRNA synthetases (ArgRSs) has evolved to have an extended N-terminal domain that plays a crucial role in protein synthesis and cell growth and in integration into the multisynthetase complex (MSC). Here, we report a crystal structure of the MSC subcomplex comprising ArgRS, glutaminyl-tRNA synthetase (GlnRS), and the auxiliary factor aminoacyl tRNA synthetase complex-interacting multifunctional protein 1 (AIMP1)/p43. In this complex, the N-terminal domain of ArgRS forms a long coiled-coil structure with the N-terminal helix of AIMP1 and anchors the C-terminal core of GlnRS, thereby playing a central role in assembly of the three components. Mutation of AIMP1 destabilized the N-terminal helix of ArgRS and abrogated its catalytic activity. Mutation of the N-terminal helix of ArgRS liberated GlnRS, which is known to control cell death. This ternary complex was further anchored to AIMP2/p38 through interaction with AIMP1. These findings demonstrate the importance of interactions between the N-terminal domains of ArgRS and AIMP1 for the catalytic and noncatalytic activities of ArgRS and for the assembly of the higher-order MSC protein complex.open111315Ysciescopu

Limits to the Rate of Adaptive Substitution in Sexual Populations

In large populations, many beneficial mutations may be simultaneously available and may compete with one another, slowing adaptation. By finding the probability of fixation of a favorable allele in a simple model of a haploid sexual population, we find limits to the rate of adaptive substitution, , that depend on simple parameter combinations. When variance in fitness is low and linkage is loose, the baseline rate of substitution is , where is the population size, is the rate of beneficial mutations per genome, and is their mean selective advantage. Heritable variance in log fitness due to unlinked loci reduces by under polygamy and under monogamy. With a linear genetic map of length Morgans, interference is yet stronger. We use a scaling argument to show that the density of adaptive substitutions depends on , , , and only through the baseline density: . Under the approximation that the interference due to different sweeps adds up, we show that , implying that interference prevents the rate of adaptive substitution from exceeding one per centimorgan per 200 generations. Simulations and numerical calculations confirm the scaling argument and confirm the additive approximation for ; for higher , the rate of adaptation grows above , but only very slowly. We also consider the effect of sweeps on neutral diversity and show that, while even occasional sweeps can greatly reduce neutral diversity, this effect saturates as sweeps become more common—diversity can be maintained even in populations experiencing very strong interference. Our results indicate that for some organisms the rate of adaptive substitution may be primarily recombination-limited, depending only weakly on the mutation supply and the strength of selection

Cracking in asphalt materials

This chapter provides a comprehensive review of both laboratory characterization and modelling of bulk material fracture in asphalt mixtures. For the purpose of organization, this chapter is divided into a section on laboratory tests and a section on models. The laboratory characterization section is further subdivided on the basis of predominant loading conditions (monotonic vs. cyclic). The section on constitutive models is subdivided into two sections, the first one containing fracture mechanics based models for crack initiation and propagation that do not include material degradation due to cyclic loading conditions. The second section discusses phenomenological models that have been developed for crack growth through the use of dissipated energy and damage accumulation concepts. These latter models have the capability to simulate degradation of material capacity upon exceeding a threshold number of loading cycles.Peer ReviewedPostprint (author's final draft

Manganese and acute paranoid psychosis: a case report

Contains fulltext : 103167.pdf (publisher's version ) (Open Access)Introduction Manganese regulates many enzymes and is essential for normal development and body function. Chronic manganese intoxication has an insidious and progressive course and usually starts with complaints of headache, fatigue, sleep disturbances, irritability and emotional instability. Later, several organ systems may be affected and, due to neurotoxicity, an atypical parkinsonian syndrome may emerge. With regard to neuropsychiatry, an array of symptoms may develop up to 30 years after intoxication, of which gait and speech abnormalities, cognitive and motor slowing, mood changes and hallucinations are the most common. Psychotic phenomena are rarely reported. Case presentation We describe the case of a 49-year-old Caucasian man working as a welder who was referred to our facility for evaluation of acute paranoid psychotic behavior. Our patient's medical history made no mention of any somatic complaints or psychiatric symptoms, and he had been involved in a professional career as a metalworker. On magnetic resonance imaging scanning of his brain, a bilateral hyperdensity of the globus pallidus, suggestive for manganese intoxication, was found. His manganese serum level was 52 to 97 nmol/L (range: 7 to 20 nmol/L). A diagnosis of organic psychotic disorder due to manganese overexposure was made. His psychotic symptoms disappeared within two weeks of treatment with low-dose risperidone. At three months later, serum manganese was decreased to slightly elevated levels and the magnetic resonance imaging T1 signal intensity was reduced. No signs of Parkinsonism were found and a definite diagnosis of manganese-induced apathy syndrome was made. Conclusion Although neuropsychiatric and neurological symptoms caused by (chronic) manganese exposure have been reported frequently in the past, in the present day the disorder is rarely diagnosed. In this report we stress that manganese intoxication can still occur, in our case in a confined-space welder, and may present clinically with a paranoid psychotic state that necessitates a rapid diagnostic procedure in order to avoid the permanent structural brain damage that may occur with chronic exposure.4 p

Efficacy of an Aspiration Prevention Program That Utilizes the Gugging Swallowing Screen in Older Patients

Ji Eun Song,1 Eunjeong Ji,2 Nak-Hyun Kim,1,3 Jung Hun Ohn,1,3 Yejee Lim,1,3 Jongchan Lee,1,3 Hye Won Kim,1,3 Sun-Wook Kim,1,3 Jiwon Ryu,1,3 Hee-Sun Park,1,3 Eun Sun Kim1,3 1Hospital Medicine Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 2Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 3Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of KoreaCorrespondence: Eun Sun Kim, Department of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Republic of Korea, Email [email protected]: Older patients have a higher risk of aspiration pneumonia and mortality if they are hospitalized. We aimed to assess the effectiveness of an aspiration prevention quality improvement (QI) program that utilizes the Gugging Swallowing Screen (GUSS) in older patients.Patients and Methods: This retrospective cohort study was conducted in an acute medical care unit of a tertiary hospital in South Korea. The study used one-to-one propensity matching and included 96 patients who received the QI program and 96 who did not. All patients were aged 65 years or older and had risk factors for aspiration, including neurological and non-neurological disorders, neuromuscular disorders, impaired airway defenses, and dysphagia due to esophageal or gastrointestinal disorders. The primary outcomes included the duration of the fasting period during hospitalization, changes in nutritional status before admission and at discharge, in-hospital mortality, and readmission due to pneumonia within 90 days.Results: Fasting period, changes in weight and albumin levels upon discharge after hospitalization, and length of stay did not differ significantly between patients in the GUSS and non-GUSS groups. However, the risk of readmission within 90 days was significantly lower in patients who underwent the GUSS than in those who did not (hazard ratio, 0.085; 95% confidence interval, 0.025– 0.290; p = 0.001).Conclusion: The GUSS aspiration prevention program effectively prevented readmission due to pneumonia within 90 days in older patients with acute illnesses. This implies that the adoption of efficient aspiration prevention methods in older patients with acute illnesses could play a pivotal role by enhancing patient outcomes and potentially mitigating the healthcare costs linked to readmissions.Keywords: aspiration pneumonia, older patients, gugging swallowing screen, prevention, quality improvemen