Salient Slices: Improved Neural Network Training and Performance with Image Entropy.

As a training and analysis strategy for convolutional neural networks (CNNs), we slice images into tiled segments and use, for training and prediction, segments that both satisfy an information criterion and contain sufficient content to support classification. In particular, we use image entropy as the information criterion. This ensures that each tile carries as much information diversity as the original image and, for many applications, serves as an indicator of usefulness in classification. To make predictions, a probability aggregation framework is applied to probabilities assigned by the CNN to the input image tiles. This technique, which we call Salient Slices, facilitates the use of large, high-resolution images that would be impractical to analyze unmodified; provides data augmentation for training, which is particularly valuable when image availability is limited; and the ensemble nature of the input for prediction enhances its accuracy.

Evaluation of the Efficiency of the Sample Inactivation Reagent in the Abbott RealTime MTB Assay for Inactivation of Mycobacterium tuberculosis.

The Abbott RealTime MTB assay is a nucleic acid amplification test (NAAT) for the detection of Mycobacterium tuberculosis complex DNA. The sample inactivation procedure used in the assay, consisting of one part sample treated with 3 parts inactivation reagent for 60 min, effectively reduced viscosity and inactivated M. tuberculosis in clinical specimens.

Toward the quantum chemical calculation of nuclear magnetic resonance chemical shifts of proteins.

Despite the many protein structures solved successfully by nuclear magnetic resonance (NMR) spectroscopy, quality control of NMR structures is still by far not as well established and standardized as in crystallography. Therefore, there is still the need for new, independent, and unbiased evaluation tools to identify problematic parts and in the best case also to give guidelines that how to fix them. We present here, quantum chemical calculations of NMR chemical shifts for many proteins based on our fragment-based quantum chemical method: the adjustable density matrix assembler (ADMA). These results show that (13)C chemical shifts of reasonable accuracy can be obtained that can already provide a powerful measure for the structure validation. (1)H and even more (15)N chemical shifts deviate more strongly from experiment due to the insufficient treatment of solvent effects and conformational averaging.

Quantification of the push-pull effect in substituted alkynes. Evaluation of +/-I/+/-M substituent effects in terms of C[triple bond]C bond length variation.

(13)C chemical shifts of alkynes, published to date, were computed at the DFT (B3LYP/6-311G*) level of theory and compared with the experimental delta values, and the agreement was employed as a measure of quality for the underlying structures. For the corresponding global minima structures, thus obtained, the occupation quotients of antibonding pi* and bonding pi orbitals (pi*(C[triple bond]C)/pi(C[triple bond]C)) and the bond lengths (d(C[triple bond]C)) of the central C[triple bond]C triple bond were computed and correlated to each other. The linear dependence obtained for the two push-pull parameters d(C[triple bond]C) and pi*(C[triple bond]C)/pi(C[triple bond]C) quantifies changes in the push-pull effect of substituents while deviations from the best line of fit indicate and ascertain quantitatively to what extend the inductive (+/-I) substituent effect changes with respect to the bond length of the C[triple bond]C triple bond.

[Nutritional status in Alzheimer's disease]. / Estado nutricional na doença de Alzheimer.

OBJECTIVE: To describe the nutritional status of elderly subjects with mild to moderate Alzheimer's disease. METHODS: Subjects of both genders (n=40) diagnosed with mild to moderate Alzheimer's disease according to NINCDS-ADRDA criteria, participated in the study. Socioeconomic status, activities of daily life, anthropometric, clinical and dietary profiles were surveyed. RESULTS: Of the total, 65% were female. More than 70% were capable of accomplishing daily activities by themselves. Subjects were eutrophic with a statistically significant difference of the arm circumference between the mild and moderate groups. As for illnesses secondary to Alzheimer's, 52% of the elderly presented hypertension, followed by arthrosis type alterations (17%). The mean consumption of energy and macronutrients in the elderly classified as mild dementia was of 1645 kcal, distributed in 53.7% of carbohydrate, 17.5% of proteins or 0.9 g/kg and 28.8% of lipids. For those classified as moderate dementia it was of 1482 kcal, distributed in 59.3% of carbohydrate, 16.1% of proteins and 24.6% of lipids. CONCLUSION: In this descriptive study of elderly outpatients with mild and moderate Alzheimer's disease, most presented a nutritional status of eutrophy, with adequate dietary intake of carbohydrates, proteins, lipids and vitamin C, but with low dietary intake of vitamin E.

Water footprint of German agricultural imports: Local impacts due to global trade flows in a fifteen-year perspective.

This study investigates the water scarcity footprint (WSF) trend of German agricultural imports over recent years, following the principles of the ISO 14046 standard on water footprinting. For this purpose, the import statistics of agricultural goods for the years 2000, 2005, 2010, and 2015 was compiled and linked with the irrigation water consumption during their production as well as with the AWARE water scarcity factors of the country of production. Agricultural imports increased by 62% from 22 to 35 million tons during the analysed period. At the same time, the blue water consumption for agricultural production (i.e., irrigation water) decreased by 13% and the WSF declined by 20%, from 119 to 91 km3world-equivalents (world-eq.). The decrease in WSF is caused by drop in the cotton imports, while the WSF associated with the imports of other crops increased by 45%. Product-wise, cotton, nuts, and rice contribute to more than half of the total WSF in all analysed years. Despite their high WSF, these products account for only 3% of the imports by mass confirming the relevance of impact based water footprint assessments. Country-wise, main contributors change along the analysed years. In the year 2000, one-quarter of the WSF occurs in Uzbekistan due to cotton imports. Afterwards, the highest WSF arises in Iran and Spain, while the imports from the US dominate the WSF in 2015. The changing trend follows the pattern of production of the hotspots identified on the product level, e.g. nuts, soybeans, and cotton. This study provides information on the water scarcity impacts that the German consumption creates in other countries and may be useful for decision-making processes aiming at optimising water scarcity footprints.

HIV-1 viral load measurement in venous blood and fingerprick blood using Abbott RealTime HIV-1 DBS assay.

BACKGROUND: HIV RNA suppression is a key indicator for monitoring success of antiretroviral therapy. From a logistical perspective, viral load (VL) testing using Dried Blood Spots (DBS) is a promising alternative to plasma based VL testing in resource-limited settings. OBJECTIVES: To evaluate the analytical and clinical performance of the Abbott RealTime HIV-1 assay using a fully automated one-spot DBS sample protocol. STUDY DESIGN: Limit of detection (LOD), linearity, lower limit of quantitation (LLQ), upper limit of quantitation (ULQ), and precision were determined using serial dilutions of HIV-1 Virology Quality Assurance stock (VQA Rush University), or HIV-1-containing armored RNA, made in venous blood. To evaluate correlation, bias, and agreement, 497 HIV-1 positive adult clinical samples were collected from Ivory Coast, Uganda and South Africa. For each HIV-1 participant, DBS-fingerprick, DBS-venous and plasma sample results were compared. Correlation and bias values were obtained. The sensitivity and specificity were analyzed at a threshold of 1000 HIV-1 copies/mL generated using the standard plasma protocol. RESULTS: The Abbott HIV-1 DBS protocol had an LOD of 839 copies/mL, a linear range from 500 to 1×107 copies/mL, an LLQ of 839 copies/mL, a ULQ of 1×107 copies/mL, and an inter-assay SD of ≤0.30 log copies/mL for all tested levels within this range. With clinical samples, the correlation coefficient (r value) was 0.896 between DBS-fingerprick and plasma and 0.901 between DBS-venous and plasma, and the bias was -0.07 log copies/mL between DBS-fingerprick and plasma and -0.02 log copies/mL between DBS-venous and plasma. The sensitivity of DBS-fingerprick and DBS-venous was 93%, while the specificity of both DBS methods was 95%. CONCLUSION: The results demonstrated that the Abbott RealTime HIV-1 assay with DBS sample protocol is highly sensitive, specific and precise across a wide dynamic range and correlates well with plasma values. The Abbott RealTime HIV-1 assay with DBS sample protocol provides an alternative sample collection and transfer option in resource-limited settings and expands the utility of a viral load test to monitor HIV-1 ART treatment for infected patients.

Associative symmetry in the pigeon after successive matching-to-sample training.

If an organism is explicitly taught an A-->B association, then might it also spontaneously learn the symmetrical B-->A association? Little evidence attests to such "associative symmetry" in nonhuman animals. We report for the first time a clear case of associative symmetry in the pigeon. Experiment 1 used a successive go/no go matching-to-sample procedure, which showed all of the training and testing stimuli in one location and intermixed arbitrary and identity matching trials. We found symmetrical responding that was as robust during testing (B-->A) as during training (A-->B). In Experiment 2, we trained different pigeons using only arbitrary matching trials before symmetry testing. No symmetrical responding was found. In Experiment 3, we trained other pigeons with only arbitrary matching trials and then tested for symmetry. When these pigeons, too, did not exhibit symmetrical responding, we retrained them with intermixed identity and arbitrary matching trials. Less robust symmetrical responding was obtained here than in Experiment 1. Collectively, these results suggest that identity matching may have to be learned concurrently with arbitrary matching from the outset of training for symmetry to emerge.

Analytical and clinical performance of Abbott RealTime MTB, an assay for detection of Mycobacterium tuberculosis in pulmonary specimens.

Nucleic acid amplification test (NAAT)-based assays provide fast and sensitive results compared to conventional TB tests. The performance of the new Abbott Molecular MTB assay for the qualitative detection of MTB complex using the automated m2000™ system or manual sample preparation is summarized in this paper. The assay detects eight MTB complex subspecies. The observed limit of detection (LOD) when used to test an MTB H37Rv panel was 2.45 colony forming units (cfu)/mL, while the claimed assay LOD with this MTB strain is 17 cfu/mL. No cross reactivity, or carryover were observed in the study. The clinical sensitivity of the assay was 93% overall; 99% in smear positive, culture positive specimens, and 81% in smear negative, culture positive samples. The clinical specificity was 97%. The inhibition rate in the study was 0.34%. The data suggest that Abbott RealTime MTB is a reliable, robust and sensitive assay for the molecular detection of MTB.

Performance attributes of the LCx HCV RNA quantitative assay.

The LCx HCV RNA quantitative assay (Abbott Laboratories, North Chicago, IL) is designed to use competitive reverse transcriptase-polymerase chain reaction (RT-PCR) and microparticle enzyme immunoassay (MEIA), in combination with a modified Qiagen sample preparation method, to measure the level of hepatitis C virus (HCV) in human plasma and serum. The assay provides quantitative results in international units (IU) of HCV RNA/ml, in copies of HCV RNA/ml, or their log (base 10) equivalents. A conversion study determined that 1IU equals 4.3 copies. The LCx HCV assay detected HCV RNA transcripts representative of genotypes 1-6 with near equal efficiency. The assay did not cross-react with high concentrations of 21 potentially cross-reactive microorganisms or with 100 HCV-negative specimens. The lower limit of detection was demonstrated to be 23IU/ml. The LCx assay had similar sensitivity to the Roche Amplicor HCV (version 2.0) qualitative assay when used to test panels containing 6, 12, 23, and 47IU/ml. The assay linear range was shown to extend from 23 to 2.3millionIU/ml. The intra-assay standard deviation (S.D.) was < or =0.066 logIU/ml for the four HCV positive samples tested, while for the same samples the observed inter-assay S.D. was < or =0.075 logIU/ml. The overall mean assay quantitation value for seven HCV-positive WHO-standardized Acrometrix NAP linearity panel members was within 0.06 logIU/ml of the mean assigned value. The assay was demonstrated to correlate acceptably against the Roche Amplicor HCV monitor test (version 2.0). These data suggest that the assay is standardized appropriately against the WHO standard across its linear range and can be used for quantitation of HCV. In addition, with a sensitivity of 23IU/ml, the assay can be used to determine if post-therapy viral clearance has occurred.

Stimulus control by same-versus-different relations among multiple visual stimuli.

The authors devised a go/no-go discrimination learning task that allowed but did not require pigeons to report (a) from which of 2 different sets a collection of visual items was drawn and (b) the relations between or among the items as being the same as or different from one another. The results of 2 experiments using this task disclosed stimulus control by the particular items in the arrays and by the same-different relations exemplified by those items. Relational and item control depended on how many items were in the arrays. Same-different discrimination was evident with 2-item displays, but it was much stronger with 6 or more items. These findings help to define the substrates of advanced conceptual behavior.

Hippocampal representation of related and opposing memories develop within distinct, hierarchically organized neural schemas.

Recent evidence suggests that the hippocampus may integrate overlapping memories into relational representations, or schemas, that link indirectly related events and support flexible memory expression. Here we explored the nature of hippocampal neural population representations for multiple features of events and the locations and contexts in which they occurred. Hippocampal networks developed hierarchical organizations of associated elements of related but separately acquired memories within a context, and distinct organizations for memories where the contexts differentiated object-reward associations. These findings reveal neural mechanisms for the development and organization of relational representations.

Toward the Quantum Chemical Calculation of NMR Chemical Shifts of Proteins. 2. Level of Theory, Basis Set, and Solvents Model Dependence.

It has been demonstrated that the fragmentation scheme of our adjustable density matrix assembler (ADMA) approach for the quantum chemical calculations of very large systems is well-suited to calculate NMR chemical shifts of proteins [ Frank et al. Proteins2011, 79, 2189-2202 ]. The systematic investigation performed here on the influences of the level of theory, basis set size, inclusion or exclusion of an implicit solvent model, and the use of partial charges to describe additional parts of the macromolecule on the accuracy of NMR chemical shifts demonstrates that using a valence triple-ζ basis set leads to large improvement compared to the results given in the previous publication. Additionally, moving from the B3LYP to the mPW1PW91 density functional and including partial charges and implicit solvents gave the best results with mean absolute errors of 0.44 ppm for hydrogen atoms excluding H(N) atoms and between 1.53 and 3.44 ppm for carbon atoms depending on the size and also on the accuracy of the protein structure. Polar hydrogen and nitrogen atoms are more difficult to predict. For the first, explicit hydrogen bonds to the solvents need to be included and, for the latter, going beyond DFT to post-Hartree-Fock methods like MP2 is probably required. Even if empirical methods like SHIFTX+ show similar performance, our calculations give for the first time very reliable chemical shifts that can also be used for complexes of proteins with small-molecule ligands or DNA/RNA. Therefore, taking advantage of its ab initio nature, our approach opens new fields of application that would otherwise be largely inaccessible due to insufficient availability of data for empirical parametrization.

Toward the Quantum Chemical Calculation of NMR Chemical Shifts of Proteins. 3. Conformational Sampling and Explicit Solvents Model.

Fragment-based quantum chemical calculations are able to accurately calculate NMR chemical shifts even for very large molecules like proteins. But even with systematic optimization of the level of theory and basis sets as well as the use of implicit solvents models, some nuclei like polar protons and nitrogens suffer from poor predictions. Two properties of the real system, strongly influencing the experimental chemical shifts but almost always neglected in the calculations, will be discussed here in great detail: (1) conformational averaging and (2) interactions with first-shell solvent molecules. Classical molecular dynamics simulations in explicit water were carried out for obtaining a representative ensemble including the arrangement of neighboring solvent molecules, which was then subjected to quantum chemical calculations. We could demonstrate with the small test system N-methyl acetamide (NMA) that the calculated chemical shifts show immense variations of up to 6 ppm and 50 ppm for protons and nitrogens, respectively, depending on the snapshot taken from a classical molecular dynamics simulation. Applying the same approach to the HA2 domain of the influenza virus glycoprotein hemagglutinin, a 32-amino-acid-long polypeptide, and comparing averaged values to the experiment, chemical shifts of nonpolar protons and carbon atoms in proteins were calculated with unprecedented accuracy. Additionally, the mean absolute error could be reduced by a factor of 2.43 for polar protons, and reasonable correlations were obtained for nitrogen and carbonyl carbon in contrast to all other studies published so far.

Recombinant reconstitution of sumoylation reactions in vitro.

Reconstituting posttranslational modification with SUMO in vitro is an essential tool in the analysis of sumoylation. In this article, we provide detailed protocols that allow to set up and perform sumoylation reactions using a purified recombinant sumoylation machinery. The protocols include purification of the SUMO E1 enzyme His-Aos1/Uba2, untagged E2 enzyme Ubc9, untagged SUMO, and the RanBP2 E3 ligase fragment IR1 + M. Using these components, we provide step-by-step instructions to set up sumoylation reactions. Two established SUMO model substrates, His-RanGAPtail and HisYFP-Sp100, complement the described tool box; these proteins serve as positive controls in E3 ligase-independent and -dependent sumoylation reactions and are valuable instruments to adjust the reaction conditions if necessary.

Development of sensitive single-round pol or env RT-PCR assays to screen for XMRV in multiple sample types.

The potential association between xenotropic murine leukemia virus-related virus (XMRV) and prostate cancer and chronic fatigue syndrome (CFS) has been much debated. To help resolve the potential role of XMRV in human disease, it is critical to develop sensitive and accurate reverse transcriptase (RT)-PCR assays to screen for the virus. Single-round RT-PCR assays were developed on the automated m2000™ system for detection of the pol or env regions of XMRV in whole blood, plasma, urine cell pellets and urogenital swab samples. Assay performance was assessed by testing two blinded panels, one comprised of whole blood and the other of plasma spiked with serial dilutions of XMRV-infected tissue culture cells and supernatant, respectively, prepared by the Blood XMRV Scientific Research Working Group (SRWG). For both whole blood and plasma panel testing, the assays showed excellent specificity and sensitivity as compared to the other tests included in the SRWG phase I study. Analytical specificity of the assays was also evaluated. Neither pol nor env PCR assays detected a panel of potential cross-reactive microorganisms, although some cross-reaction was observed with mouse genomic DNA. Screening of 196 normal human blood donor plasma, 214 HIV-1 seropositive plasma, 20 formalin-fixed paraffin-embedded (FFPE) prostate cancer specimens, 4 FFPE benign prostate specimens, 400 urine pellets from prostate cancer patients, 166 urine pellets from non-prostate cancer patients, and 135 cervical swab specimens, detected no samples as unequivocally XMRV positive.

Response rate is not an effective mediator of learned stimulus equivalence in pigeons.

We explored response rate as a possible mediator of learned stimulus equivalence. Five pigeons were trained to discriminate four clip art pictures presented during a 10-sec discrete-trial fixed interval (FI) schedule: two paired with a one-pellet reinforcer, which supported a low rate of responding, and two paired with a nine-pellet reinforcer, which supported a high rate of responding. After subjects associated one stimulus from each of these pairs with a discriminative choice response, researchers presented two new clip art stimuli during a 10-sec FI: one trained with a differential reinforcement of low rate schedule (DRL) after the FI and the other trained with a differential reinforcement of high rate schedule (DRH) after the FI. Each of the stimuli that were withheld during choice training was later shown to see if the choice responses would transfer to these stimuli. The results suggest that response rate alone does not mediate learned stimulus equivalence.

Miniavaliação nutricional na determinação do estado de saúde de idosos com ou sem a doença de alzheimer: aspectos positivos e negativos / Mini nutritional assessment in the determination of the health status of the elderly with or without Alzheimer disease: positive and negative points

A população idosa mundial vem crescendo rapidamente, o que representa um desafio para a saúde pública. A longevidade trouxe à tona doenças de natureza crônica, conseqüentes de processos degenerativos comuns ao envelhecimento. Entre estas as demências e a mais prevalente a doença de Alzheimer A DA provoca desordens cognitivas e nutricionais; a perda de apetite e de peso são sintomas que levam a implicações indesejáveis ao prognóstico da doença. Objetivou-se nesta revisão reunir estudos atuais nos quais o questionário de mini avaliação nutricional (MAN) foi utilizado na determinação do estado nutricional de idosos com ou sem a DA, considerando seus aspectos positivos e negativos. As evidências científicas ressaltam que o questionário da MAN é uma ferramenta simples e rápida na avaliação do estado nutricional de pacientes idosos em clínicas, hospitais e asilos. Estudos revisados indicam ter a MAN alta especificidade na determinação precoce do risco de desnutrição em idosos, apresentando forte correlação com resultados obtidos através de exames bioquímicos e antropométricos. Percebem-se limitações da MAN quando os idosos avaliados apresentam déficit cognitivo. As dificuldades no preenchimento da MAN devem ser reduzidas com adaptações e esclarecimentos oportunos por parte do pesquisador. Sendo assim, mais estudos devem ser realizados com a aplicação da MAN em idosos demenciados, dada a alta correlação entre estado nutricional com prognóstico da DA. Palavras chave: mini avaliação nutricional, estado nutricional, idosos, déficit cognitivo, doença de Alzheimer.

The elderly world population has been growing up quickly, which representsa public health challenge. The longevity brought up chronicdiseases, caused by degeneration problems that usually occur in elderlypeople. Dementias are beyond those diseases, especially theAlzheimer disease (AD). AD causes nutritional and cognitive disorders;low appetite and weight lost are symptoms that lead to undesirableimplications to the disease prognostic. This study objected to reviewactual studies in which the mini nutritional assessment (MNA) was appliedin the determination of the nutritional status of elderly, with orwithout AD, considering negative and positive points. Scientific evidencesshow that MNA questionnaire is a simple and quickly tool onthe nutritional assessment of elderly patients from clinics, hospitalsand nursing homes. The questionnaire permits the detection of risk ofdevelopment of malnutrition and nutrition intervention when necessary.The studies reviewed indicate a high specificity of MNA in determiningearlier the risk of malnutrition in elderly, and strong correlation betweenthe results obtained from biochemical and anthropometrics exams.Limitations are perceived in MNA when elderly assessed present cognitivedeficits. The difficulties in the filling of the MNA must be reducedwith adaptations in the questionnaire and with explanations given bythe researcher. As so, more studies should be realized with the applicationof the MNA in elderly demented, given the high correlationbetween nutritional status and AD evolution.

Estado nutricional na doença de Alzheimer / Nutritional status in Alzheimer's disease

OBJETIVO: Descrever aspectos nutricionais de idosos com doença de Alzheimer leve a moderada em ambulatório. MÉTODOS: A amostra contou com a participação de 40 idosos de ambos os sexos, diagnosticados com doença da Alzheimer (NINCDS-ADRDA) por seleção consecutiva. Foram realizadas avaliações socioeconômicas de atividades de vida diária, antropométrica, clínica e dietética. RESULTADOS: Do total, 65 por cento eram do sexo feminino. Ao se verificar a capacidade funcional, constatou-se que mais de 70 por cento dos idosos mostraram-se independentes para a realização de suas atividades de vida diária. Com base na avaliação do estado nutricional e na gravidade da doença, os idosos encontraram-se eutróficos, com diferença estatisticamente significativa na circunferência do braço entre os graus de demência. Quanto à presença de enfermidades secundárias à doença, 52 por cento dos idosos apresentaram hipertensão arterial sistêmica, seguido de alterações do tipo artrose (17 por cento). O consumo médio de energia e de macronutrientes dos idosos classificados no estágio leve foi de 1645 kcal, distribuídos em 53,7 por cento para carboidratos, 17,5 por cento para proteínas e 28,8 por cento para lipídeos, enquanto que aqueles no estágio moderado foi de 1482 kcal, distribuídos em 59,3 por cento para carboidratos, 16,1 por cento para proteínas e 24,6 por cento para lipídeos. CONCLUSÃO: Neste estudo descritivo de uma amostra ambulatorial de idosos com DA leve e moderada a maior parte deles apresentou estado nutricional de eutrofia, com consumo dietético adequado de carboidratos, proteínas, lipídeos e vitamina C, embora com baixo consumo alimentar de vitamina E.

OBJECTIVE: To describe the nutritional status of elderly subjects with mild to moderate Alzheimer's disease. METHODS: Subjects of both genders (n=40) diagnosed with mild to moderate Alzheimer's disease according to NINCDS-ADRDA criteria, participated in the study. Socioeconomic status, activities of daily life, anthropometric, clinical and dietary profiles were surveyed. RESULTS: Of the total, 65 percent were female. More than 70 percent were capable of accomplishing daily activities by themselves. Subjects were eutrophic with a statistically significant difference of the arm circumference between the mild and moderate groups. As for illnesses secondary to Alzheimer's, 52 percent of the elderly presented hypertension, followed by arthrosis type alterations (17 percent). The mean consumption of energy and macronutrients in the elderly classified as mild dementia was of 1645 kcal, distributed in 53.7 percent of carbohydrate, 17.5 percent of proteins or 0.9 g/kg and 28.8 percent of lipids. For those classified as moderate dementia it was of 1482 kcal, distributed in 59.3 percent of carbohydrate, 16.1 percent of proteins and 24.6 percent of lipids. CONCLUSION: In this descriptive study of elderly outpatients with mild and moderate Alzheimer's disease, most presented a nutritional status of eutrophy, with adequate dietary intake of carbohydrates, proteins, lipids and vitamin C, but with low dietary intake of vitamin E.