Quantum detector tomography applied to the human visual system: a feasibility study.

We show that quantum detector tomography can be applied to the human visual system to explore human perception of photon number states. In detector tomography, instead of using very hard-to-produce photon number states, the response of a detector to light pulses with known photon statistics of varying intensity is recorded, and a model is fitted to the experimental outcomes, thereby inferring the detector's photon number state response. Generally, light pulses containing a Poisson-distributed number of photons are utilized, which are very easy to produce in the lab. This technique has not been explored to study the human visual system before because it usually requires a very large number of repetitions not suitable for experiments on humans. Yet, in the present study we show that detector tomography is feasible for human experiments. Assuming a simple model for this accuracy, the results of our simulations show that detector tomography is able to reconstruct the model using Bayesian inference with as few as 5000 trials. We then optimize the experimental parameters in order to maximize the probability of showing that the single-photon accuracy is above chance. As such, our study opens the road to study human perception on the quantum level.

A high-throughput cheese manufacturing model for effective cheese starter culture screening.

Cheese making is a process in which enzymatic coagulation of milk is followed by protein separation, carbohydrate removal, and an extended bacterial fermentation. The number of variables in this complex process that influence cheese quality is so large that the developments of new manufacturing protocols are cumbersome. To reduce screening costs, several models have been developed to miniaturize the cheese manufacturing process. However, these models are not able to accommodate the throughputs required for systematic screening programs. Here, we describe a protocol that allows the parallel manufacturing of approximately 600 cheeses in individual cheese vats each with individual process specifications. Protocols for the production of miniaturized Gouda- and Cheddar-type cheeses have been developed. Starting with as little as 1.7 mL of milk, miniature cheeses of about 170 mg can be produced and they closely resemble conventionally produced cheese in terms of acidification profiles, moisture and salt contents, proteolysis, flavor profiles, and microstructure. Flavor profiling of miniature cheeses manufactured with and without mixed-strain adjunct starter cultures allowed the distinguishing of the different cheeses. Moreover, single-strain adjunct starter cultures engineered to overexpress important flavor-related enzymes revealed effects similar to those described in industrial cheese. Benchmarking against industrial cheese produced from the same raw materials established a good correlation between their proteolytic degradation products and their flavor profiles. These miniature cheeses, referred to as microcheeses, open new possibilities to study many aspects of cheese production, which will not only accelerate product development but also allow a more systematic approach to investigate the complex biochemistry and microbiology of cheese making.

Attractor crisis and bursting in a fluid flow with two no-slip directions.

Characteristic bursting behavior is observed in a driven, two-dimensional viscous flow, confined to a square domain and subject to no-slip boundaries. Passing a critical parameter value, an existing chaotic attractor undergoes a crisis, after which the flow initially enters a transient bursting regime. Bursting is caused by ejections from and return to a limited subdomain of the phase space, whereas the precrisis chaotic set forms the asymptotic attractor of the flow. For increasing values of the control parameter the length of the bursting regime increases progressively. Passing another critical parameter value, a second crisis leads to the appearance of a secondary type of bursting, of very large dynamical range. Within the bursting regime the flow then switches in irregular intervals from the primary to the secondary type of bursting. Peak enstrophy levels for both types of bursting are associated to the collapse of a primary vortex into a quadrupolar state.

Continuous measurement of the cytoplasmic pH in Lactococcus lactis with a fluorescent pH indicator.

The cytoplasmic pH of Lactococcus lactis was studied with the fluorescent pH indicator 2',7'-bis-(2-carboxyethyl)-5 (and-6)-carboxyfluorescein (BCECF). A novel method was applied for loading bacterial cells with BCECF, which consists of briefly treating a dense cell suspension with acid in the presence of the probe. This results in a pH gradient, which drives accumulation of the probe in the cytoplasm. After neutralization the probe was well retained in cells stored on ice. BCECF-loaded cells were metabolically active, and were able to generate a pH gradient upon energization. The probe leaks out slowly at elevated temperatures. Efflux is stimulated upon energization of the cells, and is most likely catalyzed by an active transport system. It is a first-order process, and the rate constant could be deduced from the decrease of the fluorescence signal in periods of constant intracellular pH. This allowed a correction of the fluorescence signal for efflux of the probe. After calibration the cytoplasmic pH could be calculated from efflux-corrected fluorescence traces.

Leukocyte chemotaxis in diabetic patients and their nondiabetic first-degree relatives.

Leukocyte chemotaxis wasmeasured in 108 subjects: 20 normal controls, 36 insulin-taking diabetics (15 being index patients), and 52 nondiabetic first-degree relatives of index patients. The relatives had a mean chemotactic index (CI) significantly lower than that of the controls (individually, 25 per cent had CIs lower than the lowest of the controls); and the diabetics had a mean CI significantly lower than that of the relatives. The impairment of leukocyte chemotaxis measured in the first-degree relatives of diabetic index patients does not appear to be associated with an increased susceptibility to infection and suggests that the impaired leukotaxis is due to an inherent defect--perhaps genetic--in leukocyte function.

Amino acid analysis using chromatography-mass spectrometry: An inter platform comparison study.

The analysis of amino acids has become a central task in many aspects. While amino acid analysis has traditionally mainly been carried out using either gas chromatography (GC) in combination with flame ionization detection or liquid chromatography (LC) with either post-column derivatization using ninhydrin or pre-column derivatization using o-phthalaldehyde, many of today's analysis platforms are based on chromatography in combination with mass spectrometry (MS). While derivatization is mandatory for the GC-based analysis of amino acids, several LC platforms have emerged, particularly in the dawn of targeted metabolite profiling using hydrophilic interaction liquid chromatography (HILIC) coupled to MS, allowing the analysis of underivatized amino acids. Among the numerous analytical platforms available for amino acid analysis today, we here compare three prominent approaches, being GC-MS and LC-MS after amino acid derivatization using chloroformate and HILIC-MS of underivatized amino acids. We compare and discuss practical issues as well as performance characteristics, e.g., the use of (13)C-labeled internal standards, of the different platforms and present data on their practical implementation in our laboratory. Finally, we compare the real-life applicability of all three platforms for a complex biological sample. While all three platforms are very-well suited for the analysis of complex biological samples they all show advantages and disadvantages for some analytes as discussed in detail in this manuscript.

Recruitment for a Diabetes Prevention Program translation effort in a worksite setting.

BACKGROUND: The success of the Diabetes Prevention Program (DPP) lifestyle intervention has led to community-based translation efforts in a variety of settings. One community setting which holds promise for the delivery of prevention intervention is the worksite; however, information regarding recruitment in this setting is limited. The current effort describes the initial processes surrounding provision of an adapted DPP lifestyle intervention at a corporate worksite. METHODS: Investigators and key management at the worksite collaborated to develop and implement a recruitment plan for the intervention focusing on 1) in-person onsite activities and 2) implementation of a variety of media recruitment tools and methods. RESULTS: Adult, non-diabetic overweight/obese employees and family members with pre-diabetes and/or the metabolic syndrome were eligible for the study. Telephone pre-screening was completed for 176 individuals resulting in 171 eligible for onsite screening. Of that number, 160 completed onsite screening, 107 met eligibility criteria, and 89 enrolled in the study. Support from worksite leadership, an invested worksite planning team and a solid recruitment plan consisting of multiple strategies were identified as crucial elements of this effective workplace recruitment effort. CONCLUSION: A worksite team successfully developed and implemented a recruitment plan using existing mechanisms appropriate to that worksite in order to identify and enroll eligible individuals. The results of this effort indicate that employee recruitment in a worksite setting is feasible as the first step in offering onsite behavioral lifestyle intervention programs as part of a widespread dissemination plan to prevent diabetes and lower risk for cardiovascular disease.

Impact of neurologic signs and symptoms on functional status in peripheral neuropathies.

OBJECTIVE: To determine whether the Neurologic Disability Score (NDS), the Neuropathic Symptom Score (NSS), and the Medical Research Council (MRC) "sumscore" are reliable, and to determine whether they provide information regarding the functional status of patients with peripheral neuropathies. METHODS: The authors analyzed homogeneity of the frequently used outcome measures in 97 patients using Cronbach's alpha coefficient and corrected item-total correlations. Their association with functional status (sickness impact profile and modified Rankin score) was analyzed univariately with Pearson's and Spearman's correlation coefficients, and multivariately with linear regression analysis. RESULTS: The NDS and MRC scales were homogeneous (range of Cronbach's alpha, 0.81 to 0.97) compared with the NSS scales (range, 0.20 to 0.63). The correlation patterns between neurologic signs and symptoms and functional status ranged from 0.13 to 0.65. Multivariate linear regression analyses showed that 40% or less of patients' functional status could be explained by the three tested outcome measures. CONCLUSION: The NDS and MRC are reliable measures, but these measures do not correlate with measures of functional status.

An additional PII in Escherichia coli: a new regulatory protein in the glutamine synthetase cascade.

The PII protein in the glutamine synthetase cascade transduces the nitrogen signal, as sensed by uridylyltransferase, both to the NRII/NRI two-component system and to adenylyltransferase, to regulate the activity of glutamine synthetase. Here we describe the amplification of a chromosomal DNA fragment from Escherichia coli which contains the sequence of a PII homologue. The derived amino acid sequence of this DNA fragment is 67% identical to E. coli PII. It contains the conserved tyrosine residue which is known to be the site of uridylylation in PII. E. coli is the first organism in which two different PII proteins have been detected.

Defining control coefficients in non-ideal metabolic pathways.

The extent to which an enzyme controls a flux has been defined as the effect on that flux of a small modulation of the activity of that enzyme divided by the magnitude of the modulation. We here show that in pathways with metabolic channelling or high enzyme concentrations and conserved moieties involving both enzymic and non-enzymic species, this definition is ambiguous; the magnitude of the corresponding flux control coefficient depends on how the enzyme activity is modulated. This is illustrated with two models of biochemically relevant pathways, one in which dynamic metabolite channelling plays a role, and one with a moiety-conserved cycle. To avoid such ambiguity, we view biochemical pathways in a more detailed manner, i.e., as a network of elemental steps. We define 'elemental control coefficients' in terms of the effect on a flux of an equal modulation of the forward and reverse rate constant of any such elemental step (which may correspond to transitions between enzyme states). This elemental control coefficient is independent of the method of modulation. We show how metabolic control analysis can proceed when formulated in terms of the elemental control coefficients and how the traditional control coefficients are related to these elemental control coefficients. An 'impact' control coefficient is defined which quantifies the effect of an activation of all elemental processes in which an enzyme is involved. It equals the sum of the corresponding elemental control coefficients. In ideal metabolic pathways this impact control coefficient reduces to the traditional flux control coefficient. Differences between the traditional control coefficients are indicative of non-ideality of a metabolic pathway, i.e. of channelling or high enzyme concentrations.

Noise suppression of transient-evoked otoacoustic emissions. I. A comparison with the non-linear method.

A new method to record transient-evoked otoacoustic emissions (TEOAEs) is introduced. Click stimuli were presented both with and without a simultaneously presented wide-band noise burst. Subtraction of the recorded signal evoked by the noise burst plus click from the signal evoked by the click alone, cancelled the eardrum reflection components of the response and resulted in a measure of the emission. This was used to obtain the TEOAEs from 21 subjects for peak click stimulus levels of 48-66 dB SPL. The root-mean-square (RMS) level of the noise burst was set 10 dB higher than the peak click level, and resulted in suppression of the TEOAE by up to 20 dB. The TEOAE waveforms obtained by the new method were compared to those obtained with Kemp's non-linear method, and were indistinguishable in 20 of the 21 subjects. On basis of the emission spectra, they were indistinguishable in 18 out of 21 subjects. The latencies of narrow-band filtered components from the TEOAEs obtained with the two methods were also similar. This suggests that this noise-suppression method produces similar results as Kemp's non-linear method with the advantage that emission components with very short latencies can be obtained.

Noise suppression of transient-evoked otoacoustic emissions. II. Derived narrow-band contributions.

Transient-evoked otoacoustic emissions (TEOAEs) were decomposed into cochlear place specific components using high-pass noise suppression. This was performed using high-pass filtered noise with cut-off frequencies between 0.7 and 5.6 kHz in 0.5-octave steps. Subtraction of the TEOAEs obtained in the presence of two high-pass noise suppressors with 0.5-octave difference in their cut-off frequencies, f(A) and f(B), should theoretically result in TEOAE components with frequencies between f(A) and f(B). The reconstructed wide-band emission power spectrum obtained by summing the narrow-band emission power spectra, was nearly identical to the power spectrum of the original wide-band emission. This suggests that no phase-cancellation occurs and that the individual narrow-band TEOAEs are uncorrelated, and thus that their generators are potentially independent. About 66% of the derived narrow-band emissions had spectral components that extended below the cut-off frequency of the lower high-pass noise filter. These tail components were interpreted as resulting from high-frequency side suppression of the high-pass noise on the click emission and potentially distortion product components from the TEOAE.

Does diisocyanate exposure result in neurotoxicity?

CONTEXT: Diisocyanates have been associated with respiratory and dermal sensitization. Limited number of case reports, and a few case studies, media, and other references suggest potential neurotoxic effects from exposures to toluene diisocyanate (TDI), 1,6 hexamethylene diisocyanate (HDI), and methylene diisocyanate (MDI). However, a systematic review of the literature evaluating the causal association on humans does not exist to support this alleged association. OBJECTIVE: To perform systematic review examining the body of epidemiologic evidence and provide assessment of causal association based on principles of the Sir Austin Bradford Hill criteria or considerations for causal analysis. METHODS: A comprehensive search of public databases for published abstracts, case reports, cross-sectional surveys, and cohort studies using key search terms was conducted. Additional searches included regulatory reviews, EU IUCLID and EU Risk Assessment databases, and unpublished reports in the International Isocyanate Institute database. An expert panel consisting of physicians, toxicologists, and an epidemiologist critically reviewed accepted papers, providing examination of epidemiologic evidence of each report. Finally, the Hill criteria for causation were applied to the summative analysis of identified reports to estimate probability of causal association. RESULTS: Twelve papers reporting exposed populations with a variety of neurological symptoms or findings suitable for analysis were identified, including eleven case or case series reports, and one cross-sectional study. Three papers reported on the same population. Each of the papers was limited by paucity of diisocyanate exposure estimates, the presence of confounding exposures to known or suspected neurotoxicants, a lack of objective biological measures of exposure or neurotoxic effects, and lack of relative strength of association measures. Additionally, reported health symptoms and syndromes lacked consistency or specificity. No plausible mechanism of toxicity was found. Application of a predictive mathematical model for determining probability of causal association for neurotoxicity was calculated to be 21%. CONCLUSION: There is insufficient evidence for a causal association of neurotoxic effects and diisocyanate exposure based on lack of evidence in all categories of the Hill criteria for causality except for temporal association of reported symptoms and alleged exposure. Future reports should attempt to address more rigorous exposure assessment and control for confounding exposures.

Pattern formation in draining thin film suspensions.

We demonstrate the emergence of complexity from remarkably simple and ubiquitous systems: draining thin-film suspensions exhibiting a striking transition between two classes of self-organizing patterns. Vertical channels form when attractive forces lead to transient gelation, while horizontal bands result from granular mixtures. We propose an explanation whereby the generic physical mechanisms require only the existence of viscous and excluded-volume couplings among the particles, solvent, and substrate. System-specific, small inhomogeneities trigger large-scale pattern formation, through collective dynamics, where jamming plays a crucial role. Our results shed light on emergent complexity in bio- and geophysical processes and have implications for coatings and food industries.

DNA micro-array-based identification of bile-responsive genes in Lactobacillus plantarum.

AIMS: The purpose of this study was to determine the global transcriptional response in a food-associated lactic acid bacterium during bile stress. METHODS AND RESULTS: Clone-based DNA micro-arrays were employed to describe the global transcriptional response of Lactobacillus plantarum WCFS1 towards 0.1% porcine bile. Comparison of differential transcript profiles obtained during growth of Lact. plantarum on plates with and without bile revealed 28 and 62 putative genes, of which the expression was at least 2.5-fold up- or down-regulated by bile, respectively. Approximately, 50% of these genes appeared genetically linked, and 12 bile-responsive gene clusters were identified. Seven of the identified bile-responsive genes and gene clusters encode typical stress-related functions, including glutathione reductase and glutamate decarboxylase, involved in oxidative and acid stress, respectively. Moreover, 14 bile-responsive genes and gene clusters were identified that encode proteins that are located in the cell envelope, including the dlt operon and the F1F0 ATPase. CONCLUSIONS: The identification of a relatively high number of genes encoding cell envelope functions indicates a major impact of bile acids on the integrity and/or functionality of the cytoplasmic membrane and cell wall. SIGNIFICANCE AND IMPACT OF THE STUDY: The data presented here provide valuable clues towards the defence mechanisms that play a role during bile stress in Lact. plantarum.

Transition to chaos in a confined two-dimensional fluid flow.

For a two-dimensional fluid in a square domain with no-slip walls, new direct numerical simulations reveal that the transition from steady to chaotic flow occurs through a sequence of various periodic and quasiperiodic flows, similar to the well-known Ruelle-Takens-Newhouse scenario. For all solutions beyond the ground state, the phenomenology is dominated by a domain-filling circulation cell, whereas the associated symmetry is reduced from the full symmetry group of the square to rotational symmetry over an angle pi. The results complement both laboratory experiments in containers with rigid walls and numerical simulations on double-periodic domains.

Functions of the membrane-associated and cytoplasmic malate dehydrogenases in the citric acid cycle of Escherichia coli.

Oxidation of malate to oxaloacetate in Escherichia coli can be catalyzed by two enzymes: the well-known NAD-dependent malate dehydrogenase (MDH; EC 1.1.1.37) and the membrane-associated malate:quinone-oxidoreductase (MQO; EC 1.1.99.16), encoded by the gene mqo (previously called yojH). Expression of the mqo gene and, consequently, MQO activity are regulated by carbon and energy source for growth. In batch cultures, MQO activity was highest during exponential growth and decreased sharply after onset of the stationary phase. Experiments with the beta-galactosidase reporter fused to the promoter of the mqo gene indicate that its transcription is regulated by the ArcA-ArcB two-component system. In contrast to earlier reports, MDH did not repress mqo expression. On the contrary, MQO and MDH are active at the same time in E. coli. For Corynebacterium glutamicum, it was found that MQO is the principal enzyme catalyzing the oxidation of malate to oxaloacetate. These observations justified a reinvestigation of the roles of MDH and MQO in the citric acid cycle of E. coli. In this organism, a defined deletion of the mdh gene led to severely decreased rates of growth on several substrates. Deletion of the mqo gene did not produce a distinguishable effect on the growth rate, nor did it affect the fitness of the organism in competition with the wild type. To investigate whether in an mqo mutant the conversion of malate to oxaloacetate could have been taken over by a bypass route via malic enzyme, phosphoenolpyruvate synthase, and phosphenolpyruvate carboxylase, deletion mutants of the malic enzyme genes sfcA and b2463 (coding for EC 1.1.1.38 and EC 1.1.1.40, respectively) and of the phosphoenolpyruvate synthase (EC 2.7.9.2) gene pps were created. They were introduced separately or together with the deletion of mqo. These studies did not reveal a significant role for MQO in malate oxidation in wild-type E. coli. However, comparing growth of the mdh single mutant to that of the double mutant containing mdh and mqo deletions did indicate that MQO partly takes over the function of MDH in an mdh mutant.

Impairment, disability, or handicap in peripheral neuropathy: analysis of the use of outcome measures in clinical trials in patients with peripheral neuropathies.

Outcome measures can be classified into measures of impairment, disability, and handicap. To investigate the biological effect of treatment, measures of impairment are appropriate. Studies investigating whether patients benefit from treatment in terms of improvement of functional health, however, require disability or handicap measures. In a review of the medical literature between 1978 and 1993, 73 controlled intervention studies in patients with peripheral neuropathies were found. Disability or handicap measures were used in two of 54 studies in patients with diabetic neuropathy, in two of six studies in patients with chronic inflammatory demyelinating polyneuropathy, in none of five studies in a mixed group of patients, and in all eight studies in patients with Guillain-Barré syndrome. The limited use of disability and handicap measures in patients with diabetic and mixed neuropathies can be explained by the experimental nature of most studies. In four of six studies, however, in patients with chronic inflammatory demyelinating polyneuropathy or neuropathy associated with monoclonal gammopathy that were designed to assess effectiveness of treatment, the choice of outcome measures was not appropriate. It is concluded that in the design of intervention studies in patients with peripheral neuropathy more attention should be paid to a proper choice of suitable outcome measures to assess the effectiveness of treatment.

Kinetic mechanism and specificity of the arginine-ornithine antiporter of Lactococcus lactis.

The kinetic mechanism and specificity of the arginine-ornithine antiporter was investigated in membrane vesicles derived from Lactococcus lactis. Membrane vesicles loaded with ornithine, and diluted into an arginine-free medium, rapidly released a limited amount of ornithine during the first seconds of incubation. The amount of ornithine released was independent of the amount initially present on the inside and roughly matched the number of ornithine-binding sites in the membrane. Net flow of ornithine was only observed in membrane vesicles derived from induced cells and blocked by p-chloromercuribenzene sulfonic acid. These results suggest that net flow of ornithine is caused by a single turnover of the antiporter. With saturating concentrations of arginine in the external medium, efflux of ornithine was stoichiometrically coupled to uptake of arginine. Arginine-ornithine exchange and net flow of ornithine are electrically silent and not regulated by the electrical potential. The kinetics of the homologous exchange reactions indicate that the Vmax values for arginine and ornithine uptake are comparable, whereas the apparent Kt values differ. No major sidedness of the apparent Kt values are observed for both surfaces of the cytoplasmic membrane. Various basic amino acid analogues, including optical isomers, are transported as well, albeit with different efficiencies (Vmax/Kt). Evidence for a competitive character of arginine and ornithine interactions for binding sites on the antiporter are provided by transport and binding measurements. The Vmax and apparent Kt for arginine uptake increases with increasing internal ornithine, with little effect on the ratio of Vmax to apparent Kt. These results are discussed in terms of a simple carrier model in which the substrate-binding site is presented alternately to the two surfaces of the membrane as in a Ping Pong mechanism for enzyme kinetics.