Empirical corrections and pair interaction energies in the fragment molecular orbital method

The energy and analytic gradient are developed for FMO combined with the Hartree-Fock method augmented with three empirical corrections (HF-3c). The auxiliary basis set approach to FMO is extended to perform pair interaction energy decomposition analysis. The FMO accuracy is evaluated for several typical systems including 3 proteins. Pair interaction energies computed with different approaches in FMO are compared for a water cluster and protein-ligand complexes.Comment: Revised version accepted in Chemical Physics Letter

A third-generation dispersion and third-generation hydrogen bonding corrected PM6 method:PM6-D3H+

We present new dispersion and hydrogen bond corrections to the PM6 method, PM6-D3H+, and its implementation in the GAMESS program. The method combines the DFT-D3 dispersion correction by Grimme et al. with a modified version of the H+ hydrogen bond correction by Korth. Overall, the interaction energy of PM6-D3H+ is very similar to PM6-DH2 and PM6-DH+, with RMSD and MAD values within 0.02 kcal/mol of one another. The main difference is that the geometry optimizations of 88 complexes result in 82, 6, 0, and 0 geometries with 0, 1, 2, and 3 or more imaginary frequencies using PM6-D3H+ implemented in GAMESS, while the corresponding numbers for PM6-DH+ implemented in MOPAC are 54, 17, 15, and 2. The PM6-D3H+ method as implemented in GAMESS offers an attractive alternative to PM6-DH+ in MOPAC in cases where the LBFGS optimizer must be used and a vibrational analysis is needed, e.g., when computing vibrational free energies. While the GAMESS implementation is up to 10 times slower for geometry optimizations of proteins in bulk solvent, compared to MOPAC, it is sufficiently fast to make geometry optimizations of small proteins practically feasible

Floral to green: mating switches moth olfactory coding and preference

Mating induces profound physiological changes in a wide range of insects, leading to behavioural adjustments to match the internal state of the animal. Here, we show for the first time, to our knowledge, that a noctuid moth switches its olfactory response from food to egg-laying cues following mating. Unmated females of the cotton leafworm (Spodoptera littoralis) are strongly attracted to lilac flowers (Syringa vulgaris). After mating, attraction to floral odour is abolished and the females fly instead to green-leaf odour of the larval host plant cotton, Gossypium hirsutum. This behavioural switch is owing to a marked change in the olfactory representation of floral and green odours in the primary olfactory centre, the antennal lobe (AL). Calcium imaging, using authentic and synthetic odours, shows that the ensemble of AL glomeruli dedicated to either lilac or cotton odour is selectively up- and downregulated in response to mating. A clear-cut behavioural modulation as a function of mating is a useful substrate for studies of the neural mechanisms underlying behavioural decisions. Modulation of odour-driven behaviour through concerted regulation of odour maps contributes to our understanding of state-dependent choice and host shifts in insect herbivores

Elongational Viscosity of Monodisperse and Bidisperse Polystyrene Melts

Submitted to J. Rheol.The startup and steady uniaxial elongational viscosity have been measured for two monodisperse polystyrene melts with molecular weights of 52 kg/mole and 103 kg/mole, and for three bidisperse polystyrene melts. The monodisperse melts show a maximum in the steady elongational viscosity vs. the elongational rate, ε, of about two times 3η_0 whereas the bidisperse melts have a maximum of up to a factor of seven times the Trouton limit of 3η_0. The Wiest model which incorporates anisotropic drag and finite extensibility may be used to interpret the results in molecular terms.Class of 1960 Fellowship Fund

A novel derivative of thioridazine shows low toxicity and efficient activity against gram‐positive pathogens

Thioridazine hydrochloride (HCl) has been suggested as a promising antimicrobial helper compound for the treatment of infections with antimicrobial-resistant bacteria. Unfortunately, the therapeutic concentration of thioridazine HCl is generally higher than what can be tolerated clinically, in part due to its toxic side effects on the central nervous system. Therefore, we aimed to synthesize a less toxic thioridazine derivative that would still retain its properties as a helper compound. This resulted in a compound designated 1-methyl-2-(2-(2-(methylthio)-10H-phenothiazin-10-yl)ethyl)-1-pentylpiperidin-1-ium bromide (abbreviated T5), which exhibited low blood–brain barrier permeability. The lowest minimal inhibitory concentration (MIC) against Staphylococcus aureus exposed to the novel compound was reduced 32-fold compared to thioridazine HCl (from 32 µg/mL to 1 µg/mL). The MIC values for T5 against five Gram-positive pathogens ranged from 1 µg/mL to 8 µg/mL. In contrast to thioridazine HCl, T5 does not act synergistically with oxacillin. In silico predictive structure analysis of T5 suggests that an acceptably low toxicity and lack of induced cytotoxicity was demonstrated by a lactate dehydrogenase assay. Conclusively, T5 is suggested as a novel antimicrobial agent against Gram-positive bacteria. However, future pharmacokinetic and pharmacodynamic studies are needed to clarify the clinical potential of this novel discovery

Health effects of omega-3,6,9 fatty acids: Perilla frutescens is a good example of plant oils

Perilla frutescens seeds are a good source of polyunsaturated fatty acids (PUFAs). The seeds of perilla are small end globular weight about 4 g/1000, contained approximately 35–45% oil. However the leaves are a very poor source of oil, since they contain only 0.2%. In addition, only the seed oil contains the omega 3 fatty acid alpha-linolenic acid (ALA). In comparing to other plant oils, perilla seed oil consistently contains the one of the highest proportion of omega-3 (ALA) fatty acids, at 54–64%. The omega-6 (linoleic acid) component is usually around 14% and omega-9 (Oleic acid) is also present in perilla oil. These polyunsaturated fatty acids are most beneficial to human health and in prevention of different diseases like cardiovascular disorders, cancer, inflammatory, rheumatoid arthritis etc

Classification of death causes after transplantation (CLASS):Evaluation of methodology and initial results

Correct classification of death causes is an important component of transplant trials.We aimed to develop and validate a system to classify causes of death in hematopoietic stem cell (HSCT) and solid organ (SOT) transplant recipients.Case record forms (CRF) of fatal cases were completed, including investigator-designated cause of death. Deaths occurring in 2010 to 2013 were used for derivation; and were validated by deaths occurring in 2013 to 2015. Underlying cause of death (referred to as recorded underlying cause) was determined through a central adjudication process involving 2 external reviewers, and subsequently compared with the Danish National Death Cause Registry.Three hundred eighty-eight recipients died 2010 to 2015 (196 [51%] SOT and 192 [49%] HSCT). The main recorded underlying causes of death among SOT and HSCT were classified as cancer (20%, 48%), graft rejection/failure/graft-versus-host-disease (35%, 28%), and infections (20%, 11%). Kappa between the investigator-designated and the recorded underlying cause of death was 0.74 (95% CI 0.69-0.80) in derivation and comparable in the validation cohort. Death causes were concordant with the Danish National Death Cause Registry in 37.2% (95% CI 31.5-42.9) and 38.4% (95% CI 28.8-48.0) in the derivation and validation cohorts, respectively.We developed and validated a method to systematically and reliably classify the underlying cause of death among transplant recipients. There was a high degree of discordance between this classification and that in the Danish National Death Cause Registry