High-Resolution Chrono-Transcriptome of Lactococcus lactis Reveals That It Expresses Proteins with Adapted Size and pI upon Acidification and Nutrient Starvation

Whole-genome transcriptional analyses performed on microorganisms are traditionally based on a small number of samples. To map transient expression variations, and thoroughly characterize gene expression throughout the growth curve of the widely used model organism Lactococcus lactis MG1363, gene expression data were collected with unprecedented time resolution. The resulting gene expression patterns were globally analyzed in several different ways to demonstrate the richness of the data and the ease with which novel phenomena can be discovered. When the culture moves from one growth phase to another, gene expression patterns change to such an extent that we suggest that those patterns can be used to unequivocally distinguish growth phases from each other. Also, within the classically defined growth phases, subgrowth phases were distinguishable with a distinct expression signature. Apart from the global expression pattern shifts seen throughout the growth curve, several cases of short-lived transient gene expression patterns were clearly observed. These could help explain the gene expression variations frequently observed in biological replicates. A method was devised to estimate a measure of unnormalized/absolute gene expression levels and used to determine how global transcription patterns are influenced by nutrient starvation or acidification of the medium. Notably, we inferred that L. lactis MG1363 produces proteins with on average lower pIs and lower molecular weights as the medium acidifies and nutrients get scarcer. IMPORTANCE This data set is a rich resource for microbiologists interested in common mechanisms of gene expression, regulation and in particular the physiology of L. lactis. Thus, similar to the common use of genome sequence data by the scientific community, the data set constitutes an extensive data repository for mining and an opportunity for bioinformaticians to develop novel tools for in-depth analysis

Constraints on a Parity-Conserving/Time-Reversal-Non-Conserving Interaction

Time-Reversal-Invariance non-conservation has now been unequivocally demonstrated in a direct measurement at CPLEAR. What about tests of time-reversal-invariance in systems other than the kaon system? Tests of time-reversal-invariance belong to two classes: searches for parity violating (P-odd)/time-reversal-invariance-odd (T-odd) interactions, and for P-even/T-odd interactions (assuming CPT conservation this implies C-conjugation non-conservation). Limits on a P-odd/T-odd interaction follow from measurements of the electric dipole moment of the neutron (with a present upper limit of 6 x 10^-26 e.cm [95% C.L.]). It provides a limit on a P-odd/T-odd pion-nucleon coupling constant which is less than 10^-4 times the weak interaction strength. Experimental limits on a P-even/T-odd interaction are much less stringent. Following the standard approach of describing the nucleon-nucleon interaction in terms of meson exchanges, it can be shown that only charged rho-meson exchange and A_1 meson exchange can lead to a P-even/T-odd interaction. The better constraints stem from measurements of the electric dipole moment of the neutron and from measurements of charge-symmetry breaking in neutron-proton elastic scattering. The latter experiments were executed at TRIUMF (497 and 347 MeV) and at IUCF (183 MeV). Weak decay experiments may provide limits which will possibly be comparable. All other experiments, like gamma decay experiments, detailed balance experiments, polarization - analyzing power difference determinations, and five-fold correlation experiments with polarized incident nucleons and aligned nuclear targets, have been shown to be at least an order of magnitude less sensitive.Comment: 15 pages LaTeX, including 5 PostScript figures. Uses ijmpe1.sty. To appear in International Journal of Modern Physics E (IJMPE). Slight change in short abstrac

Mixed integer programming model for optimizing the layout of an ICU vehicle

<p>Abstract</p> <p>Background</p> <p>This paper presents a Mixed Integer Programming (MIP) model for designing the layout of the Intensive Care Units' (ICUs) patient care space. In particular, this MIP model was developed for optimizing the layout for materials to be used in interventions. This work was developed within the framework of a joint project between the Madrid Technical Unverstity and the Medical Emergency Services of the Madrid Regional Government (SUMMA 112).</p> <p>Methods</p> <p>The first task was to identify the relevant information to define the characteristics of the new vehicles and, in particular, to obtain a satisfactory interior layout to locate all the necessary materials. This information was gathered from health workers related to ICUs. With that information an optimization model was developed in order to obtain a solution. From the MIP model, a first solution was obtained, consisting of a grid to locate the different materials needed for the ICUs. The outcome from the MIP model was discussed with health workers to tune the solution, and after slightly altering that solution to meet some requirements that had not been included in the mathematical model, the eventual solution was approved by the persons responsible for specifying the characteristics of the new vehicles. According to the opinion stated by the SUMMA 112's medical group responsible for improving the ambulances (the so-called "coaching group"), the outcome was highly satisfactory. Indeed, the final design served as a basis to draw up the requirements of a public tender.</p> <p>Results</p> <p>As a result from solving the Optimization model, a grid was obtained to locate the different necessary materials for the ICUs. This grid had to be slightly altered to meet some requirements that had not been included in the mathematical model. The results were discussed with the persons responsible for specifying the characteristics of the new vehicles.</p> <p>Conclusion</p> <p>The outcome was highly satisfactory. Indeed, the final design served as a basis to draw up the requirements of a public tender. The authors advocate this approach to address similar problems within the field of Health Services to improve the efficiency and the effectiveness of the processes involved. Problems such as those in operation rooms or emergency rooms, where the availability of a large amount of material is critical are eligible to be dealt with in a simmilar manner.</p

Probable fatal drug interaction between intravenous fenretinide, ceftriaxone, and acetaminophen: a case report from a New Approaches to Neuroblastoma (NANT) Phase I study

Background: Patients with relapsed/refractory stage 4 high-risk neuroblastoma were enrolled on a phase I study (NANT2004-03) of intravenous fenretinide emulsion. Pharmacokinetic samples were collected during and after the infusion, and the levels were measured using an HPLC system. A likely case of a fatal drug interaction between fenretinide, ceftriaxone, and acetaminophen is described, including the pharmacokinetics of fenretinide, laboratory data, and post-mortem autopsy in a pediatric neuroblastoma patient treated on this study. Case presentation: On Day 4 of a scheduled 5-day-infusion of intravenous fenretinide, the patient developed a fever, acetaminophen was started, ceftriaxone initiated for possible bacteremia, and fenretinide level doubled from 56 to 110 μM. Over the next three days, although blood cultures remained negative, the patient’s condition deteriorated rapidly. Acute liver failure was diagnosed on Day 7, and the patient expired on Day 20 of fulminant hepatic failure with associated renal, cardiac, and hemorrhagic/coagulation toxicities. Autopsy showed extensive hemorrhagic necrosis of the liver, marked bile duct proliferation, and abundant hemosiderin, consistent with cholestasis and drug toxicity. Conclusions: After extensive review of patient data, the clinical course, and the literature, we conclude that observed hepatic toxicity was likely due to a drug interaction between fenretinide and concomitant ceftriaxone and acetaminophen. None of the other 16 patients treated on this study experienced significant hepatic toxicity. Although the prevalence of cholestasis with ceftriaxone usage is relatively high, the potential drug interaction with these concomitant medications has not been previously reported. Concomitant use of fenretinide, ceftriaxone, and acetaminophen should be avoided

Sustainability indicators of a naturally ventilated photovoltaic façade system

Building Integrated Photovoltaic (BIPV) systems have been increasingly used as a means to generate electricity on-site, and their diffusion will increase in the near future. The objective of this article is to carry out a sustainability assessment of a BIPV system installed in Turkey regarding the three pillars: environmental, economic and social potential impact, in order to develop different indicators. For the socioeconomic analysis, a Multiregional Input-Output (MRIO) method was used to estimate production of goods and services, value added creation and employment opportunities. For the environmental evaluation, an Environmental Footprint (EF) analysis was performed. The levelized electricity costs and the greenhouse gas emissions abatement costs were also calculated. Results showed that the socioeconomic effects are relevant, although only a 23% of these effects remain in Turkey. The environmental profile is also good in terms of climate change impacts, showing substantial reductions in greenhouse gas emissions compared to fossil fuel alternatives for electricity generation. Regarding the life cycle stages of the technology, the highest environmental impacts are produced in the PV manufacturing processes. The electricity produced is still more costly than fossil-based technologies and in the highest range of PV technologies, but greenhouse gases abatement costs are not so high when compared to other references

A meta-analysis of the relationship between brain dopamine receptors and obesity: a matter of changes in behavior rather than food addiction?

Addiction to a wide range of substances of abuse has been suggested to reflect a ‘Reward Deficiency Syndrome'. That is, drugs are said to stimulate the reward mechanisms so intensely that, to compensate, the population of dopamine D(2) receptors (DD2R) declines. The result is that an increased intake is necessary to experience the same degree of reward. Without an additional intake, cravings and withdrawal symptoms result. A suggestion is that food addiction, in a similar manner to drugs of abuse, decrease DD2R. The role of DD2R in obesity was therefore examined by examining the association between body mass index (BMI) and the Taq1A polymorphism, as the A1 allele is associated with a 30–40% lower number of DD2R, and is a risk factor for drug addiction. If a lower density of DD2R is indicative of physical addiction, it was argued that if food addiction occurs, those with the A1 allele should have a higher BMI. A systematic review found 33 studies that compared the BMI of those who did and did not have the A1 allele. A meta-analysis of the studies compared those with (A1/A1 and A1/A2) or without (A2/A2) the A1 allele; no difference in BMI was found (standardized mean difference 0.004 (s.e. 0.021), variance 0.000, Z=0.196, P<0.845). It was concluded that there was no support for a reward deficiency theory of food addiction. In contrast, there are several reports that those with the A1 allele are less able to benefit from an intervention that aimed to reduce weight, possibly a reflection of increased impulsivity