Failing to Get the Gist: Reduced False Recognition of Semantic Associates in Semantic Dementia.

In 2 experiments involving patients with semantic dementia, the authors investigated the impact of semantic memory loss on both true and false recognition. Experiment 1 involved recognition memory for categories of everyday objects that shared a predominantly semantic relationship. The patients showed preserved item-specific recollection for the pictorial stimuli but, compared with control participants, exhibited significantly reduced utilization of gist information regarding the categories of objects. The latter result is consistent with the patients' degraded semantic knowledge. Experiment 2 involved categories of abstract objects that were related to one another perceptually rather than semantically. Patients with semantic dementia obtained item-specific recollection and gist memory scores that were indistinguishable from those of control participants. These results suggest that the reduction in gist memory in semantic dementia is largely specific to semantic representations and cannot be attributed to general difficulty with abstracting and/or utilizing gistlike commonalities between stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intraspecies variability in the dose-response relationship for Salmonella Enteritidis associated with genetic differences in cellular immune response

To evaluate the effects of differences in host cellular immunity, we studied the dose-response relationship for infection with Salmonella enterica serovar Enteritidis (SE) in two different rat strains, skewed towards T helper 1 (Th1, Lewis rats) or T helper 2 (Th2, Brown Norway rats) immunoregulation. Rats were exposed orally to different doses of SE after overnight starvation and neutralization of gastric acid. Animals were observed for clinical signs of disease, fecal excretion and SE load in spleen and cecum, histopathology of the cecum, hematology, and cellular and humoral immune responses. Exponential dose-response models were used for binary or continuous outcomes to analyze the experimental data. Cytokine patterns, antibody isotypes, and contact hypersensitivity tests confirmed that Lewis rats are Th1 prone, whereas Brown Norway rats are Th2 prone. The probability of infection per single SE cell was approximately 100 times higher in Brown Norway rats than in Lewis rats. Cellular immune responses were more pronounced in Lewis rats but antibody responses were higher in Brown Norway rats. When infected, colonization levels and inflammation are highest in the intestinal tract of Th2 skewed rats, but systemic infection is more intense in Th1 skewed rats. Successful colonization by only one or two SE clones resulted in a marked increase of neutrophil counts by a factor of two to three in both rat strains.     

Implications of the dependence of the elastic properties of DNA on nucleotide sequence

Recent advances in structural biochemistry have provided evidence that not only the geometric properties but also the elastic moduli of duplex DNA are strongly dependent on nucleotide sequence in a way that is not accounted for by classical rod models of the Kirchhoff type. A theory of sequence-dependent DNA elasticity is employed here to calculate the dependence of the equilibrium configurations of circular DNA on the binding of ligands that can induce changes in intrinsic twist at a single base-pair step. Calculations are presented of the influence on configurations of the assumed values and distribution along the DNA of intrinsic roll and twist and a modulus coupling roll to twist. Among the results obtained are the following. For minicircles formed from intrinsically straight DNA, the distribution of roll-twist coupling strongly affects the dependence of the total elastic energy Psi on the amount alpha of imposed untwisting, and that dependence can be far from quadratic. (In fact, for a periodic distribution of roll-twist coupling with a period equal to the intrinsic helical repeat length, Psi can be essentially independent of alpha for -90 degrees < alpha <90 degrees.) When the minicircle is homogeneous and without roll-twist coupling, but with uniform positive intrinsic roll, the point at which Psi attains its minimum value shifts towards negative values of alpha. It is remarked that there are cases in which one can relate graphs of Psi versus alpha to the 'effective values' of bending and twisting moduli and helical repeat length obtained from measurements of equilibrium distributions of topoisomers and probabilities of ring closure. For a minicircle formed from DNA that has an 'S' shape when stress-free, the graphs of Psi versus alpha have maxima at alpha = 0. As the binding of a twisting agent to such a minicircle results in a net decrease in Psi, the affinity of the twisting agent for binding to the minicircle is greater than its affinity for binding to unconstrained DNA with the same sequence.     

Fluidized bed micro-machining and HFCVD of diamond films onto Co-cemented tungsten carbide (WC-Co) hardmetal slabs

The effect of fluidized bed (FB) treatment upon hot filament chemical vapor deposition (HFCVD) of polycrystalline diamond films onto WC-Co hardmetal substrates was investigated. Several scenarios to make the substrates ready for HFCVD were, comparatively, evaluated and the resulting diamond films were examined in terms of their morphology and adhesion. The diamond grain density was measured by scanning electron microscopy. The adhesion of continuous diamond film to substrate was evaluated by the reciprocal of the slope of crack radius-indentation load functions. Surface binder dissolution followed by FB treatment (PF pretreatment) allowed very high diamond nucleation density and smaller grain size. The adhesion of films grown on PF pretreated substrates was found to be very close to that of films deposited on hardmetal slabs pretreated by Murakami's reagent followed by Co etching with Caro's acid and seeded with diamond suspension in an ultrasonic vessel (MPS pretreatment). However, diamond coatings on MPS pretreated samples exhibited a rougher surface morphology as a result of both lower diamond nucleation density and larger substrate surface roughening by Murakami's etching. Based upon experimental findings, our newly developed PF pretreatment was found to be a very promising technique in substrates conditioning as well as in promoting adherent, uniform and smooth diamond coatings onto hardmetal tools and wear parts.     

6-Substituted pyrrolo[3,4-c]pyrazoles: an improved class of CDK2 inhibitors

We have recently reported a new class of CDK2/cyclin A inhibitors based on a bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. The introduction of small alkyl or cycloalkyl groups in position 6 of this scaffold allowed variation at the other two diversity points. Conventional and polymer-assisted solution phase chemistry provided a way of generating compounds with improved biochemical and cellular activity. Optimization of the physical properties and pharmacokinetic profile led to a compound which exhibited good efficacy in vivo on A2780 human ovarian carcinoma.     

Biological sulphate removal from industrial effluent in an upflow packed bed reactor

A biological process for the removal of sulphate, using molasses as organic carbon source, is described. Sulphate is converted to sulphur via sulphide, and molasses to bicarbonate. Sulphate reducing bacteria are responsible for the reduction of sulphate to sulphide, while photosynthetic sulphur bacteria oxidize sulphide to elemental sulphur. It has been shown that these bacteria can live symbiotically in an upflow anaerobic packed bed reactor. The process is accompanied by the precipitation of calcium carbonate and heavy metal sulphides. Sulphate reduction follows zero order kinetics with respect to both reactants and products. The reduction of 1 g sulphate consumes 1.2 ml molasses and requires 6 h for completion. The optimum temperature for sulphate reduction was found to be 31°C.     

Application of the antimony trichloride-spectrophotometric method to the determination of gossypol in cottonseed and cottonseed products

Summary A method is described which permits application of the antimony trichloride spectrophotometric method to the determination of gossypol in a variety of cottonseed products. Gossypol is determined by means of the following series of operations: 1. extraction of gossypol from cottonseed or cottonseed products by use of chloroform or aqueous ethanol; 2. isolation of gossypol from the extracts by use of aqueous alkali; and 3. application of the antimony trichloride-spectrophotometric test. Data are presented to show the results obtained by application of this procedure to the determination of gossypol in pigment glands, raw cottonseed meats, cooked cottonseed meats, hydraulic- and screw-pressed meals, solvent-extracted meals, gland-free meals, and oils, both expressed and solvent-extracted. Presented at the 39th Annual meeting of the American Oil Chemists' Society in New Orleans, May 4–6, 1948. One of the laboratories of the Bureau of Agricultural and Industrial Chemistry, Agricultural Research Administration, U. S. Department of Agriculture.     

Asymmetric Disulfanylbenzamides as Irreversible and Selective Inhibitors of Staphylococcus aureus Sortase A

Staphylococcus aureus is one of the most frequent causes of nosocomial and community-acquired infections, with drug-resistant strains being responsible for tens of thousands of deaths per year. S. aureus sortase A inhibitors are designed to interfere with virulence determinants. We have identified disulfanylbenzamides as a new class of potent inhibitors against sortase A that act by covalent modification of the active-site cysteine. A broad series of derivatives were synthesized to derive structure-activity relationships (SAR). In vitro and in silico methods allowed the experimentally observed binding affinities and selectivities to be rationalized. The most active compounds were found to have single-digit micromolar K_i values and caused up to a 66 % reduction of S. aureus fibrinogen attachment at an effective inhibitor concentration of 10 μM. This new molecule class exhibited minimal cytotoxicity, low bacterial growth inhibition and impaired sortase-mediated adherence of S. aureus cells.     

The effect of bovine viral diarrhea virus introduction on milk production of Dutch dairy herds

Dairy cows are negatively affected by the introduction of bovine viral diarrhea virus (BVDV), and consequently, produce less milk. Existing literature on potential milk production losses is based on relatively outdated data and hardly evaluates milk production loss in relation to a new BVDV infection in a surveillance system. This study determined the annual and quarterly loss in milk production of BVDV introduction in 3,126 dairy herds participating in the Dutch BVDV-free program between 2007 and 2017. Among these herds, 640 were “breakdown-herds” that obtained and subsequently lost their BVDV-free status during the study period, and 2,486 herds obtained and retained their BVDV-free status during the study period. Milk yields before and after BVDV introduction were compared through annual and quarterly linear mixed models. The fixed variables for both models included herd type (breakdown-herd or free-herd), bovine viral diarrhea status (on an annual and quarterly basis), year, season, and a random herd effect. The dependent variable was the average daily milk yield on the test day. To define the possible BVDV-introduction dates, 4 scenarios were developed. In the default scenario, the date of breakdown (i.e., loss of the BVDV-free status) was assumed as the BVDV-introduction date. For the other 3 scenarios, the BVDV-introduction dates were set at 4, 6, and 9 mo before the date of breakdown, based on the estimated birth date of a persistently infected calf. In the default scenario, the loss in milk yield due to BVDV introduction occurred mainly in the first year after breakdown, with a reduction in yield of 0.08 kg/cow per day compared with the last year before breakdown. For the other 3 scenarios, the greatest yield reduction occurred in the second year after BVDV introduction, with a loss of 0.09, 0.09, and 0.1 kg/cow per day, respectively. For the first 4 quarters after BVDV introduction in the default scenario, milk yield loss was 0.14, 0.09, 0.02, and 0.08 kg/cow per day, respectively. These quarterly results indicated that milk yield loss was greatest in the first quarter after BVDV introduction. Overall, BVDV introduction had a negative, but on average a relatively small, effect on milk yield for herds participating in the BVDV-free program. This study will enable dairy farmers and policymakers to have a clearer understanding of the quantitative milk production effect of BVDV on dairy farms in a control program.