Probing Computation in the Primate Visual System at Single-Cone Resolution.

Daylight vision begins when light activates cone photoreceptors in the retina, creating spatial patterns of neural activity. These cone signals are then combined and processed in downstream neural circuits, ultimately producing visual perception. Recent technical advances have made it possible to deliver visual stimuli to the retina that probe this processing by the visual system at its elementary resolution of individual cones. Physiological recordings from nonhuman primate retinas reveal the spatial organization of cone signals in retinal ganglion cells, including how signals from cones of different types are combined to support both spatial and color vision. Psychophysical experiments with human subjects characterize the visual sensations evoked by stimulating a single cone, including the perception of color. Future combined physiological and psychophysical experiments focusing on probing the elementary visual inputs are likely to clarify how neural processing generates our perception of the visual world.

Designed miniaturization of microfluidic biosensor platforms using the stop-flow technique.

Here, we present a novel approach to increase the degree of miniaturization as well as the sensitivity of biosensor platforms by the optimization of microfluidic stop-flow techniques independent of the applied detection technique (e.g. electrochemical or optical). The readout of the labeled bioassays, immobilized in a microfluidic channel, under stop-flow conditions leads to a rectangular shaped peak signal. Data evaluation using the peak height allows for a high level miniaturization of the channel geometries. To study the main advantages and limitations of this method by numerical simulations, a universally applicable model system is introduced for the first time. Consequently, proof-of-principle experiments were successfully performed with standard and miniaturized versions of an electrochemical biosensor platform utilizing a repressor protein-based assay for tetracycline antibiotics. Herein, the measured current peak heights are the same despite the sextuple reduction of the channel dimensions. Thus, this results in a 22-fold signal amplification compared to the constant flow measurements in the case of the miniaturized version.

Surveillance of infant pertussis in Sweden 1998-2012; severity of disease in relation to the national vaccination programme.

In Sweden, pertussis was excluded from the national vaccination programme in 1979 until acellular vaccination was introduced in a highly endemic setting in 1996. The general incidence dropped 10-fold within a decade, less in infants. Infant pertussis reached 40-45 cases per 100,000 in 2008 to 2012; few of these cases were older than five months. We present an observational 15-year study on the severity of infant pertussis based on 1,443 laboratory-confirmed cases prospectively identified from 1998 to 2012 in the national mandatory reporting system and followed up by telephone contact. Analyses were made in relation to age at onset of symptoms and vaccination history. Pertussis decreased in non-vaccinated infants (2003 to 2012, p<0.001), indicating herd immunity, both in those too young to be vaccinated and those older than three months. The hospitalisation rates also decreased (last five-year period vs the previous five-year periods, p <0.001), but 70% of all cases in under three month-old infants and 99% of cases with apnoea due to pertussis were admitted to hospital in 1998 to 2012. Median duration of hospitalisation was seven days for unvaccinated vs four days for vaccinated infants aged 3-5 months. Nine unvaccinated infants died during the study period.

Final analysis and results of the Phase II SIMPLE dark matter search.

We report the final results of the Phase II SIMPLE measurements, comprising two run stages of 15 superheated droplet detectors each, with the second stage including an improved neutron shielding. The analyses include a refined signal analysis, and revised nucleation efficiency based on a reanalysis of previously reported monochromatic neutron irradiations. The combined results yield a contour minimum of σp=5.7×10(-3) pb at 35 GeV/c2 in the spin-dependent sector of weakly interacting massive particle (WIMP) proton interactions, the most restrictive to date for MW}≤60 GeV/c2 from a direct search experiment and overlapping, for the first time, with results previously obtained only indirectly. In the spin-independent sector, a minimum of 4.7×10(-6) pb at 35 GeV/c2 is achieved, with the exclusion contour challenging a significant part of the light mass WIMP region of current interest.

Two geographically separated food-borne outbreaks in Sweden linked by an unusual Cryptosporidium parvum subtype, October 2010.

The number of sporadic cases of Cryptosporidium identified in the Stockholm county area increased above the expected limit during October 2010. Additionally, two food-borne outbreaks of cryptosporidiosis occurred in two other Swedish cities: Umeå (4 October) and Örebro (9 October). The outbreak investigations did not reveal any responsible food item, however fresh herbs were suspected. Thirty stool samples, originating from all three events, tested positive for Cryptosporidium oocysts. Polymerase chain reaction (PCR) and subsequent restriction fragment length polymorphism (RFLP) revealed that 27 individuals were infected with C. parvum, two with C. hominis, and one with C. felis. Using sequence analysis of the GP60 glycoprotein gene, a polymorphic marker with high intra-species diversity, we identified the same C. parvum subtype IIdA24G1 in samples from both the Umeå outbreak and the Stockholm area cases, thus indicating a possible outbreak in the Stockholm area and establishing a link between these two events. C. parvum IIdA24G1 has not previously been described in connection with a food-borne outbreak. For the outbreak in Örebro, another subtype was identified: C. parvum IIdA20G1e. These findings demonstrate that subtyping C. parvum isolates using GP60 gene amplification can be used to link cases in an outbreak investigation and we recommend its use in future similar events.

Uncus and amiygdala lesions: effects on social behavior in the free-ranging rhesus monkey.

The eflect of uncinectomny on the social behavior of free-ranging rhesus monkeys was observed on Cayo Santiago Island. Operated subjects showed social indifjerence, failed to display appropriate aggressive and submissive gestures. were expelled from their social group, and evenitlually died. Two juvenile subjects with the lesion restricted to amygdala survived and have rejoinied their social group. Size of lesion and age at operation were major factors in determniting the degree of behavioral change.

Behavior of free-ranging macaques after intraventricular 6-hydroxydopamine.

Macaques (Macaca mulatta) observed in a free-ranging colony on Guayacan Island, Puerto Rico, were significantly different in their social interactions, initiatives, facial expressions, and postures after intraventricular 6-hydroxydopamine compared with sham-treated and field controls. This study extends the known effects of 6-hydroxydopamine and catecholamine depletion to the social interactions of a higher primate species under free-ranging conditions.

Social behavior of monkeys selectively depleted of monoamines.

Initiated social interactions of Macaca speciosa are decreased during the period of treatment with alpha-methyl-p-tyrosine, an inhibitor of catecholamine synthesis. The treated animals maintained stable body weights and appeared to be healthy. Similar depletion of indoleamines with p-chlorophenylalanine does not change these same observed behaviors in spite of weight loss, hair loss, ataxia, and debilitation in some of the animals.

Genetic variations in the serotonin 5-HT2A receptor gene (HTR2A) are associated with rheumatoid arthritis.

OBJECTIVES: To analyse the association between the genetic polymorphisms within the HTR2A gene for the serotonin receptor and rheumatoid arthritis (RA). METHODS: HTR2A gene polymorphisms were analysed in patients with RA and controls from two study populations using PCR based restriction endonuclease mapping or TaqMan allelic discrimination with more than 4000 individuals included in the current study. RESULTS: At the discovery stage we detected significant differences in frequency of rs6313 (T102C polymorphism) between the patients with RA and controls (p = 0.006). Following validation with an extended set of single nucleotide polymorphisms (SNPs) and number of DNA samples, a trend in associations in allelic model for SNPs rs6314, rs1328674, rs6313 and rs6311 (p = 0.006, 0.002, 0.006, 0.009) was seen, although it was lost after correction for multi-comparison for all but rs1328674 (empirical p value = 0.021). However, haplotype frequency analysis based on these four SNPs showed significantly low representation of TCTT combination in patients with RA in comparison with controls (3.6% and 5.6%, p<0.001 on chi(2) test, empirical p = 0.004 after 100 000 permutations) and a significantly higher frequency of CTCC combination in patients with RA in comparison with controls (3.6% and 2.2%, p = 0.002 on chi(2) test, empirical p = 0.022 after 100 000 permutations). CONCLUSIONS: In our study, genetic polymorphisms at the HTR2A gene are associated with susceptibility for RA, suggesting possible links between the serotonergic system and development of the disease.

APPLICATION OF DROPLET DETECTORS TO ALPHA RADIATION DETECTION.

Superheated droplet detectors (SDDs) are traditionally employed in the detection of neutrons. In this work the focus is on the detection of alpha particles using C2ClF5 as the target liquid. The alpha-droplet interaction is examined via computational studies, and a geometric model developed to describe the expected detector response. Experiments with alpha-emitting uranium- and samarium-doped SDDs at temperatures of 5-12°C confirm that the event rate is related to the size of the droplets, and are in model agreement for temperatures below 8°C; above this temperature, the acoustic sensitivity is reduced by signal attenuation as a result of the increasing bubble population, for which the addition of an attenuation coefficient restores the agreement with experiment. The results suggest the viability of a SDD-based alpha spectrometer using mono-sized droplets.

Clinical on-site monitoring of ß-lactam antibiotics for a personalized antibiotherapy.

An appropriate antibiotherapy is crucial for the safety and recovery of patients. Depending on the clinical conditions of patients, the required dose to effectively eradicate an infection may vary. An inadequate dosing not only reduces the efficacy of the antibiotic, but also promotes the emergence of antimicrobial resistances. Therefore, a personalized therapy is of great interest for improved patients' outcome and will reduce in long-term the prevalence of multidrug-resistances. In this context, on-site monitoring of the antibiotic blood concentration is fundamental to facilitate an individual adjustment of the antibiotherapy. Herein, we present a bioinspired approach for the bedside monitoring of free accessible ß-lactam antibiotics, including penicillins (piperacillin) and cephalosporins (cefuroxime and cefazolin) in untreated plasma samples. The introduced system combines a disposable microfluidic chip with a naturally occurring penicillin-binding protein, resulting in a high-performance platform, capable of gauging very low antibiotic concentrations (less than 6 ng ml-1) from only 1 µl of serum. The system's applicability to a personalized antibiotherapy was successfully demonstrated by monitoring the pharmacokinetics of patients, treated with ß-lactam antibiotics, undergoing surgery.

Estimation of 99Mo production rates from natural molybdenum in research reactors.

Molybdenum-99 is one of the most important radionuclides for medical diagnostics. In 2015, the International Atomic Energy Agency organized a round-robin exercise where the participants measured and calculated specific saturation activities achievable for the 98Mo(n,γ)99Mo reaction. This reaction is of interest as a means to locally, and on a small scale, produce 99Mo from natural molybdenum. The current paper summarises a set of experimental results and reviews the methodology for calculating the corresponding saturation activities. Activation by epithermal neutrons and also epithermal neutron self-shielding are found to be of high importance in this case.

Dosimetry at the Portuguese research reactor using thermoluminescence measurements and Monte Carlo calculations.

This work presents an extensive study on Monte Carlo radiation transport simulation and thermoluminescent (TL) dosimetry for characterising mixed radiation fields (neutrons and photons) occurring in nuclear reactors. The feasibility of these methods is investigated for radiation fields at various locations of the Portuguese Research Reactor (RPI). The performance of the approaches developed in this work is compared with dosimetric techniques already existing at RPI. The Monte Carlo MCNP-4C code was used for a detailed modelling of the reactor core, the fast neutron beam and the thermal column of RPI. Simulations using these models allow to reproduce the energy and spatial distributions of the neutron field very well (agreement better than 80%). In the case of the photon field, the agreement improves with decreasing intensity of the component related to fission and activation products. (7)LiF:Mg,Ti, (7)LiF:Mg,Cu,P and Al(2)O(3):Mg,Y TL detectors (TLDs) with low neutron sensitivity are able to determine photon dose and dose profiles with high spatial resolution. On the other hand, (nat)LiF:Mg,Ti TLDs with increased neutron sensitivity show a remarkable loss of sensitivity and a high supralinearity in high-intensity fields hampering their application at nuclear reactors.

Self-assembled magnetic bead chains for sensitivity enhancement of microfluidic electrochemical biosensor platforms.

In this paper, we present a novel approach to enhance the sensitivity of microfluidic biosensor platforms with self-assembled magnetic bead chains. An adjustable, more than 5-fold sensitivity enhancement is achieved by introducing a magnetic field gradient along a microfluidic channel by means of a soft-magnetic lattice with a 350 µm spacing. The alternating magnetic field induces the self-assembly of the magnetic beads in chains or clusters and thus improves the perfusion and active contact between the analyte and the beads. The soft-magnetic lattices can be applied independent of the channel geometry or chip material to any microfluidic biosensing platform. At the same time, the bead-based approach achieves chip reusability and shortened measurement times. The bead chain properties and the maximum flow velocity for bead retention were validated by optical microscopy in a glass capillary. The magnetic actuation system was successfully validated with a biotin-streptavidin model assay on a low-cost electrochemical microfluidic chip, fabricated by dry-film photoresist technology (DFR). Labelling with glucose oxidase (GOx) permits rapid electrochemical detection of enzymatically produced H2O2.

EEG power variation in schizophrenic subgroups: effects of emotionally salient stimuli.

Eighteen unmedicated chronic schizophrenic patients and 13 normal controls were tested in a paradigm designed to examine functional changes in electroencephalographic (EEG) activity following presentation of emotionally salient auditory stimuli and control tones. Five standard bands of EEG spectral power were examined at bilateral frontal and temporal surface recording sites. The schizophrenic subjects were assigned to diagnostic subgroups on the basis of DSM-III-R criteria following independent clinical examination by two staff psychiatrists. Those subjects who met DSM-III-R criteria for paranoid schizophrenia were assigned to one subgroup (PS subgroup), while those who met DSM-III-R criteria for either residual or undifferentiated schizophrenia were assigned to a second subgroup (R/US subgroup). Analysis of Variance of EEG activity recorded at bilateral frontal (F1 and F2) and temporal (T3 and T4) scalp leads revealed significant diagnosis-related differences in alpha and beta-2 activity at temporal recording sites, and in beta-1 and beta-2 activity at frontal recording sites. Post-hoc tests revealed that significant differences in all four measures occurred in the R/US subgroup, which showed a decrease in temporal alpha and an increase in temporal beta-2 power as compared to controls. These variations in EEG activity appeared to demonstrate a degree of subgroup specificity, as the R/US subgroup also differed significantly from the PS subgroup on most of these measures. Significant subgroup-specific lateralization effects were also observed for temporal lobe delta activity and for frontal lobe beta-1 activity. These findings are interpreted in terms of subgroup-specific alterations in the processing of sensory information in schizophrenia, particularly when such information is emotionally salient. They suggest that subgroup differences in emotional and clinical state may be reflected in differential changes in EEG spectra within the schizophrenic population.

Glutathione peroxidase and CT scan abnormalities in schizophrenia.

The search for morphological clues to the etiology of schizophrenia has led to widespread application of computed tomography (CT) scans in the examination of patients. These investigations have resulted in numerous reports over the past several years of brain atrophy and increased ventricle-brain ratios (VBR), suggestive of neuronal tissue damage, associated with the disorder. Altered activity of cellular antioxidant systems have been implicated in the neuronal cell loss that is associated with degenerative diseases of the central nervous system (CNS), but this phenomenon has not been investigated with respect to functional disorders like schizophrenia. A search for such a relationship in schizophrenics with evidence of brain atrophy has been initiated by measuring the activity of the important antioxidant enzyme glutathione peroxidase (GPx) in blood samples from a population of chronic schizophrenics and age- and sex-matched nonschizophrenic mental patients as controls. A strong negative correlation has been found between GPx activity in both isolated platelets and erythrocytes and CT scan measures of brain atrophy and VBR in the schizophrenics, but not in the control population, which exhibited comparable CT scan abnormalities. These observations suggest a unique relationship of GPx to the mechanism of tissue damage in the schizophrenics.

Phosphatidylserine inhibition of monoamine oxidase in platelets of schizophrenics.

Phosphatidylserine (PS) has recently been reported to be a specific inhibitor of B-type monoamine oxidase (MAO-B). The effect of added PS liposomes on platelet MAO-B activity was examined in two schizophrenic groups (paranoid and a mixture of residual/undifferentiated) and in normal controls. PS was a potent partial-mixed-uncompetitive inhibitor of the platelet enzyme, whereas other phospholipids tested were without effect. The PS concentration required for 50% inhibition was significantly higher for the paranoid relative to the residual/undifferentiated group and controls. This correlated with a lower mean basal MAO-B activity in this group. Hill plots, as a measure of the concentration dependence of PS sensitivity, however, revealed a similarity between the two schizophrenic groups in regard to inhibitor binding properties. Mean Hill coefficients for both groups were significantly different from the controls. The results were consistent with an in vivo role for PS as an allosteric regulator of platelet MAO-B.

Oral tacrine administration in middle-aged monkeys: effects on discrimination learning.

We studied the effect of chronic, oral administration of 1,2,3,4 tetrahydro-9-aminoacridine (THA), an anticholinesterase, on the acquisition of a color discrimination task in five monkeys (Macaca radiata), aged 13-19 years. A two-phase experiment was performed: initially, one animal was used and served as his own control in a multiple dose, crossover, placebo controlled trial, designed to establish a dose-response curve and an optimal dose range based on THA serum concentrations. Thereafter, four monkeys were given the optimal dose of THA (5.0 mg/day) determined previously while learning up to four color pair discriminations. They also learned up to four other color pair discriminations while on placebo. Two monkeys received THA first, then placebo; the others received placebo first, then THA. No order effects were noted. When combined scores for THA tests were compared to their placebo scores, the difference was significant at p less than 0.01 with all four THA treated monkeys requiring fewer trials to reach learning criterion. These results indicate that THA has a significantly positive effect on the acquisition of a color discrimination task.

Serum alpha 1-antichymotrypsin level as a marker for Alzheimer-type dementia.

Excessive alpha 1-antichymotrypsin (ACT) in brain has been postulated to play a role in the pathogenesis of Alzheimer's disease (AD). We measured serum ACT by radial immunodiffusion in 57 patients with presumed AD, 110 healthy controls (24 children; 86 adults), 67 non-AD patients from a geriatric private practice and a VA nursing home, and 136 asthmatics (56 adults; 80 children) as an inflammatory disease control group. Serum ACT was significantly higher in AD (73.1 +/- 22 mg/dl) than in healthy controls (47.9 +/- 8.1 mg/dl) or non-AD patients (61.8 +/- 23.9 mg/dl). A level of 60 mg/dl best separated AD patients from controls or non-AD patients. Serial measurements served to distinguish elevations of ACT level in AD from non-AD inflammatory conditions; the ACT level in the latter returned to normal with therapy or time, but the levels in AD remained elevated. A measure of serum ACT by radial immunodiffusion can be used to support a diagnosis of AD disease but not necessarily as a screening test due to the potentially large number of false positives (26% in the population studied) should malignancy or inflammatory disease be concurrent.