Disentangling the impact of Atlantic Niño on sea-air CO2 flux.

Atlantic Niño is a major tropical interannual climate variability mode of the sea surface temperature (SST) that occurs during boreal summer and shares many similarities with the tropical Pacific El Niño. Although the tropical Atlantic is an important source of CO2 to the atmosphere, the impact of Atlantic Niño on the sea-air CO2 exchange is not well understood. Here we show that the Atlantic Niño enhances (weakens) CO2 outgassing in the central (western) tropical Atlantic. In the western basin, freshwater-induced changes in surface salinity, which considerably modulate the surface ocean CO2 partial pressure (pCO2), are the primary driver for the observed CO2 flux variations. In contrast, pCO2 anomalies in the central basin are dominated by the SST-driven solubility change. This multi-variable mechanism for pCO2 anomaly differs remarkably from the Pacific where the response is predominantly controlled by upwelling-induced dissolved inorganic carbon anomalies. The contrasting behavior is characterized by the high CO2 buffering capacity in the Atlantic, where the subsurface water mass contains higher alkalinity than in the Pacific.

BioBits™ Bright: A fluorescent synthetic biology education kit.

Synthetic biology offers opportunities for experiential educational activities at the intersection of the life sciences, engineering, and design. However, implementation of hands-on biology activities in classrooms is challenging because of the need for specialized equipment and expertise to grow living cells. We present BioBits™ Bright, a shelf-stable, just-add-water synthetic biology education kit with easy visual outputs enabled by expression of fluorescent proteins in freeze-dried, cell-free reactions. We introduce activities and supporting curricula for teaching the central dogma, tunable protein expression, and design-build-test cycles and report data generated by K-12 teachers and students. We also develop inexpensive incubators and imagers, resulting in a comprehensive kit costing

Tissue iron deficiency and adiposity-related inflammation in disadvantaged preschoolers from NE Brazil.

BACKGROUND/OBJECTIVES: Earlier we reported an association between iron deficiency and overweight in Brazilian preschoolers. Here, we investigate whether this is the result of adipose-related inflammation. SUBJECTS/METHODS: Fasting serum C-reactive protein, α-1-acid glycoprotein (AGP), hepcidin, interleukin-6 (IL-6) and leptin, together with two iron biomarkers (serum ferritin and transferrin receptor (sTfR)), were measured in 364 disadvantaged preschoolers with a mean BMIZ (standardised Z-score for BMI) of 0.015, aged 3-6 years and attending day care in Salvador, Brazil. The role of genetic haemoglobin (Hb) disorders, intestinal parasites and dietary iron supply (calculated from serving sizes of 20 weekday menus) were also examined. RESULTS: Forty-eight children (13%) were overweight (BMIZ >1). Prevalence of tissue iron deficiency (sTfR >113.3 nmol/l; 30.6 vs 12.5%; P=0.002) and chronic inflammation (AGP >25 µmol/l; 19 vs 10%; P=0.025) were higher in overweight than in normal-weight children. From multiple regression, BMIZ was a positive predictor of log serum sTfR, ferritin and leptin, but not of log hepcidin or IL-6. Instead, major positive predictors of log hepcidin were log IL-6, followed by an elevated AGP and sex (male), whereas for log IL-6 elevated AGP was the only significant predictor. Besides BMIZ, sex (female) was also a major positive predictor of leptin. Heterozygous variant of sickle cell Hb (n=20), but not helminths, was also a positive predictor of log sTfR. Median dietary iron supply (mg/day) was above the WHO Recommended Nutrient Intake assuming moderate bioavailability and appeared adequate. CONCLUSIONS: The role of adiposity-related inflammation in tissue iron deficiency should be considered even when the prevalence of overweight is relatively low.

First results from the LUX dark matter experiment at the Sanford underground research facility.

The Large Underground Xenon (LUX) experiment is a dual-phase xenon time-projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota). The LUX cryostat was filled for the first time in the underground laboratory in February 2013. We report results of the first WIMP search data set, taken during the period from April to August 2013, presenting the analysis of 85.3 live days of data with a fiducial volume of 118 kg. A profile-likelihood analysis technique shows our data to be consistent with the background-only hypothesis, allowing 90% confidence limits to be set on spin-independent WIMP-nucleon elastic scattering with a minimum upper limit on the cross section of 7.6 × 10(-46) cm(2) at a WIMP mass of 33 GeV/c(2). We find that the LUX data are in disagreement with low-mass WIMP signal interpretations of the results from several recent direct detection experiments.

Poor dietary quality of complementary foods is associated with multiple micronutrient deficiencies during early childhood in Mongolia.

OBJECTIVE: To assess whether persistent micronutrient deficiencies in Mongolian children identified in our earlier biochemical study are associated with inadequacies in quantity and/or quality in their complementary diets. DESIGN: A cross-sectional study of breast-fed children aged 6-23 months, randomly selected from four districts in Ulaanbaatar and four provincial capitals. SUBJECTS: Weight and length were measured, and sociodemographic status, feeding practices and nutrient adequacy of complementary foods for children aged 6-8 months (n 26), 9-11 months (n 29) and 12-23 months (n 73) were assessed via questionnaire and in-home interactive 24 h recalls. RESULTS: No geographic differences existed so data were combined. Adherence to WHO infant and young child feeding practices was poor: few children were exclusively breast-fed up to 6 months of age or received the recommended number of feedings containing the recommended number of food groups. Nevertheless, energy intakes from complementary diets, primarily from cereals and non-nutritious snacks, were above WHO-estimated needs; <1 % of energy was from meat and eggs or fruits and vegetables. Median intakes and densities of most nutrients (except protein, thiamin and riboflavin) failed to meet WHO recommendations for at least two age groups, assuming average breast milk intake; greatest density deficits were for Fe > vitamin C > vitamin A > Zn > Ca. CONCLUSIONS: Complementary feeding in Mongolia is compromised by deficits in several micronutrients but not energy, in part because of frequent consumption of non-nutritious snacks. The latter may interfere with breast-feeding and should be avoided. Instead, wheat-based complementary foods should be enriched with affordable cellular animal foods and fruits rich in vitamin C to combat existing micronutrient deficits.

Understanding of informed consent and surgeon liability by the public and patients.

PURPOSE: To evaluate understanding of the fundamental concepts of informed consent by the public and patients. METHODS: Questionnaires were distributed to any persons (aged more than 16 years) attending the Palmerston North Hospital (excluding in-patients). The first 1000 completed questionnaires were analysed using the Chi squared test. RESULTS: The fundamental concepts of informed consent were not appreciated by most respondents; only 18%, 13%, and 5% of them agreed with its implications in terms of self-autonomy, confidentiality, and battery, respectively. 64% of respondents preferred to take sole responsibility to decide which procedure to undergo, 31% preferred to be guided by the surgeon, and 5% by a brief explanation only. 21% of the respondents considered the surgeon liable in the event of an unmentioned rare complication, 43% considered the surgeon not liable, and 34% were undecided. CONCLUSION: Understanding of medico-legal implications of informed consent (e.g. self-autonomy, confidentiality, and battery) by the public and patients is poor. Their expectations regarding self-autonomy seem unrealistic. It is time for surgeons, legal experts, and the public to confer and make informed consent a practical, user-friendly tool rather than the legal obstacle that it is today.

Impact of engineering flow conditions on plasmid DNA yield and purity in chemical cell lysis operations.

Chemical lysis of bacterial cells using an alkaline solution containing a detergent may provide an efficient scalable means for selectively removing covalently closed circular plasmid DNA from high-molecular-weight contaminating cellular components including chromosomal DNA. In this article we assess the chemical lysis of E. coli cells by SDS in a NaOH solution and determine the impact of pH environment and shear on the supercoiled plasmid and chromosomal DNA obtained. Experiments using a range of plasmids from 6 kb to 113 kb determined that in an unfavorable alkaline environment, where the NaOH concentration during lysis is greater than 0.15 +/- 0.03 M (pH 12.9 +/- 0.2), irreversible denaturation of the supercoiled plasmid DNA occurs. The extent of denaturation is shown to increase with time of exposure and NaOH concentration. Experiments using stirred vessels show that, depending on NaOH concentration, moderate to high mixing rates are necessary to maximize plasmid yield. While NaOH concentration does not significantly affect chromosomal DNA contamination, a high NaOH concentration is necessary to ensure complete conversion of chromosomal DNA to single-stranded form. In a mechanically agitated lysis reactor the correct mixing strategy must balance the need for sufficient mixing to eliminate potential regions of high NaOH concentrations and the need to avoid excessive breakage of the shear sensitive chromosomal DNA. The effect of shear on chromosomal DNA is examined over a wide range of shear rates (10(1)-10(5) s(-1)) demonstrating that, while increasing shear leads to fragmentation of chromosomal DNA to smaller sizes, it does not lead to significantly increased chromosomal DNA contamination except at very high shear rates (about 10(4)-10(5) s(-1)). The consequences of these effects on the choice of lysis reactor and scale-up are discussed.

Quantification of proteins and metabolites by mass spectrometry without isotopic labeling or spiked standards.

A new method is presented for quantifying proteomic and metabolomic profile data by liquid chromatography-mass spectrometry (LC-MS) with electrospray ionization. This biotechnology provides differential expression measurements and enables the discovery of biological markers (biomarkers). Work presented here uses human serum but is applicable to any fluid or tissue. The approach relies on linearity of signal versus molecular concentration and reproducibility of sample processing. There is no use of isotopic labeling or chemically similar standard materials. Linear standard curves are reported for a variety of compounds introduced into human serum. As a measure of analytical reproducibility for proteome and metabolome sampling, median coefficients of variation of 25.7 and 23.8%, respectively, were determined for approximately 3400 molecular ions (not counting their numerous isotopes) from 25 independently processed human serum samples, corresponding to a total of 85000 individual molecular ion measurements.

Gaulin homogenization: a mechanistic study.

Free radical-based oxidation has been detected in the normal operating regime of the Gaulin homogenizer, demonstrating that cavitation occurs in this important industrial bioprocessing equipment. Free radical generation is suppressed by imposition of back pressure, proving that such cavitation occurs in the impingement section. The calculated value of the cavitation number is consistent with submerged jet cavitation, wherein a high-speed jet exiting from the valve gap accelerates fluid in the impingement region, creating the vacuum conditions for cavitation. Using polysaccharides as a model shear-sensitive compound, their breakage pattern in the homogenizer was characterized by molecular size and polydispersity and compared to those of fluid shear flows in capillary tubes and cavitating flow from a sonic horn. The results indicate that breakage occurs primarily by fluid shear, although a contribution by cavitation is also apparent when back pressure is applied. Because biological molecules can readily react with free radicals and the alterations caused thereby are subtle in nature, a thorough evaluation of the impact of free radicals in upstream homogenization is warranted.

Stability of gentamicin sulfate and tobramycin sulfate in extemporaneously prepared ophthalmic solutions at 8 degrees C.

The stability of gentamicin sulfate and tobramycin sulfate in fortified ophthalmic solutions stored under refrigeration was studied. Fortified gentamicin ophthalmic solution and fortified tobramycin ophthalmic solution were prepared to a final theoretical concentration of 13.6 mg/mL by using commercially available ophthalmic and injectable solutions. Volumes of each solution were packaged in plastic bottles and refrigerated at 4-8 degrees C. Samples of each solution were analyzed by fluorescence polarization immunoassay on days 0 (before refrigeration), 1, 2, 3, 4, 7, 14, 28, 63, and 91. To validate the method, identical solutions were prepared, stored under refrigeration at 4-8 degrees C, and analyzed by a stability-indicating high-performance liquid chromatographic assay on days 0 (before refrigeration), 9, 28, 56, and 91. Fluorescence polarization immunoassay showed the mean concentrations of gentamicin and tobramycin on day 91 to be 104.4% and 97.4%, respectively, of the time 0 concentrations; the difference was not significant in either case. HPLC validated these results; the mean concentration of gentamicin and tobramycin on day 91 was 103.3% and 101.2%, respectively, of the mean day 0 concentrations. Gentamicin and tobramycin in ophthalmic solutions prepared by mixing ophthalmic and injectable products and stored in plastic bottles at 4-8 degrees C were stable for three months.

Pharmacokinetic comparison of 5 g of azlocillin every 8 h and 4 g every 6 h in healthy volunteers.

To compare the multiple-dose pharmacokinetics of two dosage regimens of azlocillin, we studied 12 healthy volunteers via a randomized, crossover design with a 2-week washout phase between regimens. Serum and urine samples were collected for 8 h following the fifth dose of a regimen of 4 g every 6 h and the fourth dose of a regimen of 5 g every 8 h. Data for concentrations in serum were fitted to a two-compartment open model by nonlinear regression. Statistically significant differences (P less than 0.05) were observed in the following parameters (mean +/- standard deviation) for the 4- and 5-g regimens, respectively: area under the serum concentration-time curve during the dosing interval, 592 +/- 140 versus 772 +/- 151 micrograms.h/ml; terminal elimination rate constant, 0.5364 +/- 0.0912 versus 0.4758 +/- 0.0486 h-1; renal clearance, 87.6 +/- 16.1 versus 76.1 +/- 13.5 ml/min; maximum drug concentration in serum, 381 +/- 89 versus 473 +/- 90 micrograms/ml; and minimum drug concentration in serum, 19 +/- 10 versus 8 +/- 4 micrograms/ml. No significant differences were seen in the following parameters: V1, V beta, k10, k12, k21, total systemic clearance, and nonrenal clearance. These data support the presence of saturable renal elimination of azlocillin, as well as the feasibility of an 8-h dosing interval.

Phenytoin-induced hypersensitivity reactions.

A case of phenytoin-induced hepatitis with mononucleosis is reported, and syndromes associated with phenytoin hypersensitivity reactions are discussed. A 23-year-old black woman with a two-month history of seizure disorder was admitted to a hospital with nausea, vomiting, fever, lymphadenopathy, diffuse maculopapular rash, left-upper-quadrant tenderness, and hepatomegaly. She was receiving phenytoin sodium 300 mg/day; carbamazepine 200 mg four times daily had been discontinued four days before admission because of leukopenia. Phenytoin was discontinued after admission; however, phenytoin 1 g i.v. was given for a tonic-clonic seizure two days after admission, after which swelling of the face and legs and pruritus developed. Over the next few days, signs and symptoms of hepatotoxicity progressed, and she became comatose. Seizures were treated with diazepam. She began to recover after 10 days of supportive therapy and was discharged several weeks later on primidone therapy. Serious phenytoin hypersensitivity reactions may appear as dermatologic, lymphoid, or hepatic syndromes. Fever, rash, and lymphadenopathy often accompany hepatic injury. Encephalopathy and death may occur. Proposed mechanisms for phenytoin hypersensitivity include antigen-antibody reactions, alteration of lymphocyte function, and an enzyme abnormality causing the production of toxic metabolites. Treatment is supportive; phenobarbital and carbamazepine may be used with caution as alternate anticonvulsant therapy. The possibility of phenytoin hypersensitivity reactions should be considered when patients receiving phenytoin have unusual symptoms, particularly fever, rash, and lymphadenopathy.

Massive cerebral calcifications associated with increased renal phosphate reabsorption.

Extensive bilateral cerebral cortical calcifications were demonstrated in a young patient with a history of convulsions since the age of 4 years. Initial metabolic workup showed normal serum calcium levels, hyperphosphatemia, normal renal function, low urinary calcium excretion, and normal serum immunoreactive parathyroid hormone levels. The intravenous infusion of edetate disodium (disodium EDTA) showed a normal phosphaturic and cyclic adenosine monophosphate response, ruling out the diagnosis of pseudohypoparathyroidism. The infusion of acetazolamide produced a blunted phosphaturia with almost no change in the renal phosphorus threshold, suggesting a tubular defect that allows enhanced proximal tubular reabsorption of phosphorus. Although the exact mechanisms responsible for the localized calcifications remain obscure, we suggest that an enhanced proximal tubular reabsorption of phosphorus could be involved in the pathophysiologic basis of this abnormality.

The effect of in-line filtration on tobramycin delivery.

The purpose of this study was to determine if the presence of an in-line 0.22 mu cellulose ester membrane filter would hamper the delivery of a common adult dose of tobramycin sulfate. Solutions of tobramycin sulfate 80 mg in 100 ml D5W were assayed after 30 minute infusions through unfiltered and filtered administration sets; solutions post-flush of filtered sets were also assayed. Assay was done by Emit-QST. The results indicated that there was no significant difference in the delivery of tobramycin sulfate, regardless of the presence of an in-line filter. Solutions post-flush contained about ten percent of the drug, reflecting the amount in solution that remained in the tubing. Since ten percent can alter pharmacokinetic monitoring for patient dosing, a consistent procedure for flushing filtered administration sets should be adopted to enhance accuracy of such determinations.

Scleral discoloration associated with long-term prednisone administration.

A case of scleral thinning and discoloration associated with long-term prednisone administration to a patient with systemic lupus erythematosus is reported. Other medications which can cause this discoloration were not found in the history. The clinician should be aware of this complication.