The challenge of modeling nuclear receptor regulatory networks in mammalian cells.

Nuclear receptors are a major component of signal transduction in animals. They mediate the regulatory activities of many hormones, nutrients and metabolites on the homeostasis and physiology of cells and tissues. It is of high interest to model the corresponding regulatory networks. While molecular and cell biology studies of individual promoters have provided important mechanistic insight, a more complex picture is emerging from genome-wide studies. The regulatory circuitry of nuclear receptor regulated gene expression networks, and their response to cellular signaling, appear highly dynamic, and involve long as well as short range chromatin interactions. We review how progress in understanding the kinetics and regulation of cofactor recruitment, and the development of new genomic methods, provide opportunities but also a major challenge for modeling nuclear receptor mediated regulatory networks.

BAL9141, a novel extended-spectrum cephalosporin active against methicillin-resistant Staphylococcus aureus in treatment of experimental endocarditis.

The therapeutic efficacy of BAL9141 (formerly Ro 63-9141), a novel cephalosporin with broad in vitro activity that also has activity against methicillin-resistant Staphylococcus aureus (MRSA), was investigated in rats with experimental endocarditis. The test organisms were homogeneously methicillin-resistant S. aureus strain COL transformed with the penicillinase-encoding plasmid pI524 (COL Bla+) and homogeneously methicillin-resistant, penicillinase-producing isolate P8-Hom, selected by serial exposure of parent strain P8 to methicillin. The MICs of BAL9141 for these organisms (2 mg/liter) were low, and BAL9141was bactericidal in time-kill curve studies after 24 h of exposure to either two, four, or eight times the MIC. Rats with experimental endocarditis were treated in a three-arm study with a continuous infusion of BAL5788 (formerly Ro 65-5788), a carbamate prodrug of BAL9141, or with amoxicillin-clavulanate or vancomycin. The rats were administered BAL9141 to obtain steady-state target levels of 20, 10, and 5 mg of per liter or were administered either 1.2 g of amoxicillin-clavulanate (ratio 5:1) every 6 h or 1 g of vancomycin every 12 h at changing flow rates to simulate the pharmacokinetics produced in humans by intermittent intravenous treatment. Treatment was started 12 h after bacterial challenge and lasted for 3 days. BAL9141 was successful in the treatment of experimental endocarditis due to either MRSA isolate COL Bla+ or MRSA isolate P8-Hom at the three targeted steady-state concentrations and sterilized >90% of cardiac vegetations (P < 0.005 versus controls; P < 0.05 versus amoxicillin-clavulanate and vancomycin treatment groups). These promising in vivo results with BAL9141 correlated with the high affinity of the drug for PBP 2a and its stability to penicillinase hydrolysis observed in vitro.

Effect of Lactobacillus paracasei ST11 on a nasal provocation test with grass pollen in allergic rhinitis.

Cite this as: J. Wassenberg, S. Nutten, R. Audran, N. Barbier, V. Aubert, J. Moulin, A. Mercenier and F. Spertini, Clinical & Experimental Allergy, 2011 (41) 565-573. SUMMARY: Background Probiotics have been associated with prevention and improvement of symptoms in atopic diseases such as atopic dermatitis. However, few studies exist that document their efficacy for upper airways allergies such as allergic rhinitis. Objective To investigate the effect of short-term oral administration of Lactobacillus paracasei ST11 on a nasal provocation test (NPT) with grass pollen. Methods Thirty-one adult volunteers with allergic rhinitis were enrolled in a randomized, double-blind, placebo-controlled study, based on two 4-week cross-over periods of product consumption (ST11-fermented milk vs. placebo), separated by a wash-out period of 6-8 weeks. Objective and subjective clinical parameters of NPT as well as systemic and nasal immunological parameters were compared between the two treatment periods (registration number: NCT 011 50 253). Results Subjects that received ST11-fermented milk had lower nasal congestion than subjects under placebo (visual analogical scale; P<0.05). Nasal pruritus followed the same trend. However, no significant change in combined nasal reaction threshold was observed between the two periods. IL-5 secretion by peripheral blood mononuclear cells and serum allergen-specific IgG4 were significantly lower in ST11-fermented milk group compared to placebo group. IL-8 and IL-10 secretion followed the same trend. Conclusion and Clinical Relevance Short-term treatment with ST11-fermented milk before NPT significantly improved a clinical marker of NPT (subjective nasal congestion) and down-regulated systemic immune markers (IL-5 from peripheral blood mononuclear cells and serum IgG4). These data strongly suggest that probiotics may down modulate key parameters of allergic rhinitis and warrant future evaluation in seasonal trials.

Evalution of Hot Mix Asphalt Moisture Sensitivity Using the Nottingham Asphalt Test Equipment, July 2005

Moisture sensitivity of Hot Mix Asphalt (HMA) mixtures, generally called stripping, is a major form of distress in asphalt concrete pavement. It is characterized by the loss of adhesive bond between the asphalt binder and the aggregate (a failure of the bonding of the binder to the aggregate) or by a softening of the cohesive bonds within the asphalt binder (a failure within the binder itself), both of which are due to the action of loading under traffic in the presence of moisture. The evaluation of HMA moisture sensitivity has been divided into two categories: visual inspection test and mechanical test. However, most of them have been developed in pre-Superpave mix design. This research was undertaken to develop a protocol for evaluating the moisture sensitivity potential of HMA mixtures using the Nottingham Asphalt Tester (NAT). The mechanisms of HMA moisture sensitivity were reviewed and the test protocols using the NAT were developed. Different types of blends as moisture-sensitive groups and non-moisture-sensitive groups were used to evaluate the potential of the proposed test. The test results were analyzed with three parameters based on performance character: the retained flow number depending on critical permanent deformation failure (RFNP), the retained flow number depending on cohesion failure (RFNC), and energy ratio (ER). Analysis based on energy ratio of elastic strain (EREE ) at flow number of cohesion failure (FNC) has higher potential to evaluate the HMA moisture sensitivity than other parameters. If the measurement error in data-acquisition process is removed, analyses based on RFNP and RFNC would also have high potential to evaluate the HMA moisture sensitivity. The vacuum pressure saturation used in AASHTO T 283 and proposed test has a risk to damage specimen before the load applying.

VIDEO TEST

VIDEO TEST

Motivation, Test Scores, and Economic Success

This paper argues that low-stakes test scores, available in surveys, may be partially determined by test-taking motivation, which is associated with personality traits but not with cognitive ability. Therefore, such test score distributions may not be informative regarding cognitive ability distributions. Moreover, correlations, found in survey data, between high test scores and economic success may be partially caused by favorable personality traits. To demonstrate these points, I use the coding speed test that was administered without incentives to National Longitudinal Survey of Youth 1979 (NLSY) participants. I suggest that due to its simplicity its scores may especially depend on individuals' test-taking motivation. I show that controlling for conventional measures of cognitive skills, the coding speed scores are correlated with future earnings of male NLSY participants. Moreover, the coding speed scores of highly motivated, though less educated, population (potential enlists to the armed forces) are higher than NLSY participants' scores. I then use controlled experiments to show that when no performance-based incentives are provided, participants' characteristics, but not their cognitive skills, affect effort invested in the coding speed test. Thus, participants with the same ability (measured by their scores on an incentivized test) have significantly different scores on tests without performance- based incentives.

Learn about the Land - A Geologic Guide to the RAGBRAI Challenge, July 2006

Thie bourchure that is produced by the Iowa Geological Society, talks about points of interest to people that are biking accross Iowa. Part of RAGBRAI.

Behavioral Assumptions and Management Ability: A Tentative Test

The paper explores the consequences that relying on different behavioral assumptions in training managers may have on their future performance. We argue that training with an emphasis on the standard assumptions used in economics (rationality and self-interest) leads future managers to rely excessively on rational and explicit safeguarding, crowding out instinctive contractual heuristics and signaling a 'bad' type to potential partners. In contrast, human assumptions used in management theories, because of their diverse, implicit and even contradictory nature, do not conflict with the innate set of cooperative tools and may provide a good training ground for such tools. We present tentative confirmatory evidence by examining how the weight given to behavioral assumptions in the core courses of the top 100 business schools influences the average salaries of their MBA graduates. Controlling for the average quality of their students and some other schools' characteristics, average salaries are significantly greater for those schools whose core MBA courses contain a higher proportion of management courses as opposed to courses based on economics or technical disciplines.

Ordonnance de sortie d'hôpital: un défi pour la continuité des soins et la collaboration interprofessionnelle [Hospital's discharge prescription: a challenge for continuity of care and the interprofessional collaboration].

The transition between hospital and community is an interface at high risk for medication. "The Association of Family Doctors" committee in the canton of Vaud (MFVaud), together with community pharmacists' and Homecare representatives, have begun to consider the following improvements: fast and co-ordinated care providers' information; arrangements for family doctors appointments as soon as possible; awareness and education for interprofessional collaboration; more secured preparation of pill boxes; development of interprofessional means such as medication use reviews and reconciliations. In the opinion of all the experts, there is an urgent public health need to act in an interprofessional manner, even if the solutions required (especially change in professional culture and technologies) are not immediate.

Evaluation of neuromotor development by means of the Harris Infant Neuromotor Test

Objective: To investigate the neuromotor development of at-risk children between three and 12 months of life, administering the Brazilian version of the Harris Infant Neuromotor Test (HINT).Method: A longitudinal study, with 78 children and 76 parents/guardians discharged from a neonatal intensive care unit in Fortaleza-CE/Brazil. Two instruments were administered: HINT and a socioeconomic questionnaire, between July/2009 to August/2010. Data from 55 preterm and 23 term children were analyzed. Results: The final mean scores ranged from 14.6 to 25.2 and from 11.2 to 24.7, for preterm and term, respectively, showing that 91% of children demonstrated good neuromotor performance; seven premature infants showed alterations which led to the referral of three children to a specialized clinic for examination and diagnostics.Conclusion: The test allowed nurses to assess infant development, identify deviations early, and plan interventions.

Use of alcohol in the elderly: transcultural validation of the Michigan Alcoholism Screening Test – Geriatric Version (MAST-G)

Objective: To evaluate the internal consistency of the version of the Michigan Alcoholism Screening Test – Geriatric Version (MAST-G) instrument, translated and adapted for Brazil. Method: This was a descriptive, cross-sectional study. Data were collected through a demographic questionnaire, the ICD-10 and the MAST-G, following the steps of translation and cultural adaptation. One hundred eleven elderly in the city of São Carlos, SP, Brazil were interviewed. Results: The mean age of those interviewed was 70 years, with 45% men and 55% women, with the mean education of three years; 92% resided with family; 48% of the subjects consumed alcoholic beverages. The MAST-G presented a good level of reliability, with Cronbach’s α = 0.7873, and good levels of sensitivity and specificity with a cutoff score of five positive responses. Conclusion: The Brazilian version of the MAST-G presented internal consistency values similar to the original English version,showing it to be adequate for use in the national context.