Frequency domain near-infrared multiwavelength imager design using high-speed, direct analog-to-digital conversion

Frequency domain near-infrared spectroscopy (FD-NIRS) has proven to be a reliable method for quantification of tissue absolute optical properties. We present a full-sampling direct analog-to-digital conversion FD-NIR imager. While we developed this instrument with a focus on high-speed optical breast tomographic imaging, the proposed design is suitable for a wide-range of biophotonic applications where fast, accurate quantification of absolute optical properties is needed. Simultaneous dual wavelength operation at 685 and 830 nm is achieved by concurrent 67.5 and 75 MHz frequency modulation of each laser source, respectively, followed by digitization using a high-speed (180  MS/s) 16-bit A/D converter and hybrid FPGA-assisted demodulation. The instrument supports 25 source locations and features 20 concurrently operating detectors. The noise floor of the instrument was measured at <1.4  pW/√Hz, and a dynamic range of 115+ dB, corresponding to nearly six orders of magnitude, has been demonstrated. Titration experiments consisting of 200 different absorption and scattering values were conducted to demonstrate accurate optical property quantification over the entire range of physiologically expected values.United States. National Institutes of Health (R01-CA142575)United States. National Institutes of Health (R01-CA097305)United States. National Institutes of Health (R01-CA187595)United States. National Institutes of Health (R00-EB011889

Species-specific evolution of immune receptor tyrosine based activation motif-containing CEACAM1-related immune receptors in the dog

Background: Although the impact of pathogens on the evolution of the mammalian immune system is still under debate, proteins, which both regulate immune responses and serve as cellular receptors for pathogens should be at the forefront of pathogen-driven host evolution. The CEA ( carcinoembryonic antigen) gene family codes for such proteins and indeed shows tremendous species-specific variation between human and rodents. Since little is known about the CEA gene family in other lineages of placental mammals, we expected to gain new insights into the evolution of the rapidly diverging CEA family by analyzing the CEA family of the dog. Results: Here we describe the complete CEA gene family in the dog. We found that the gene coding for the ITIM-bearing immunoregulatory molecule CEACAM1 gave rise to a recent expansion of the canine CEA gene family by gene duplication, similar to that previously found in humans and mice. However, while the murine and human CEACAMs (carcinoembryonic antigen-related cell adhesion molecules) are predominantly secreted and GPI-anchored, respectively, in the dog, most of the CEACAMs represent ITAM-bearing transmembrane proteins. One of these proteins, CEACAM28, exhibits nearly complete sequence identity with the ligand-binding N domain of CEACAM1, but antagonizing signaling motifs in the cytoplasmic tail. Comparison of nonsynonymous and synonymous substitutions indicates that the CEACAM28 N domain is under the strongest purifying selection of all canine CEACAM1-related CEACAMs. In addition, CEACAM28 shows a similar expression pattern in resting immune cells and tissues as CEACAM1. However, upon activation CEACAM28 mRNA and CEACAM1 mRNA are differentially regulated. Conclusion: Thus, CEACAM1 and CEACAM28 are the first paired immune receptors identified within the CEA gene family, which are expressed on T cells and are most likely involved in the fine-tuning of T cell responses. The direction of gene conversion accompanied by purifying selection and expression in immune cells suggests the possibility that CEACAM28 evolved in response to selective pressure imposed by species-specific pathogens

Oxygen superstructures throughout the phase diagram of (Y,Ca)Ba2Cu3O6+x\bf (Y,Ca)Ba_2 Cu_3 O_{6+x}

Short-range lattice superstructures have been studied with high-energy x-ray diffuse scattering in underdoped, optimally doped, and overdoped $\rm (Y,Ca)Ba_2 Cu_3 O_{6+x}$. A new four-unit-cell superstructure was observed in compounds with $x\sim 0.95$. Its temperature, doping, and material dependence was used to attribute its origin to short-range oxygen vacancy ordering, rather than electronic instabilities in the $\rm CuO_2$ layers. No significant diffuse scattering is observed in YBa$_2$Cu$_4$O$_{8}$. The oxygen superstructures must be taken into account when interpreting spectral anomalies in $\rm (Y,Ca)Ba_2 Cu_3 O_{6+x}$

Beam heat load and pressure rise in a cold vacuum chamber

The beam heat load and the pressure in the vacuum chamber of the cold bore superconducting undulator installed at ANKA (ANgstrom source KArlsruhe) have been monitored for almost two years. Possible sources of the observed heat load could be synchrotron radiation from upstream magnets, image currents, electron and ion bombardment. In this paper, the various possible contributions to the heat load are discussed and compared with experimental results. The dynamic pressure increases nonlinearly with the average beam current. The current where it assumes a maximum varies both with the bunch intensity and with the initial vacuum pressure. A correlation between the heat load and the dynamic pressure has been observed. This study suggests that electron bombardment could explain the beam heat load and pressure rise observed for a bunch length of 10 mm

Beam heat load and pressure rise in a could vacuum chamber

The beam heat load and the pressure in the vacuum chamber of the cold bore superconducting undulator installed at ANKA (ANgstrom source KArlsruhe) have been monitored for almost two years. Possible sources of the observed heat load could be synchrotron radiation from upstream magnets, image currents, electron and ion bombardment. In this paper, the various possible contributions to the heat load are discussed and compared with experimental results. The dynamic pressure increases nonlinearly with the average beam current. The current where it assumes a maximum varies both with the bunch intensity and with the initial vacuum pressure. A correlation between the heat load and the dynamic pressure has been observed. This study suggests that electron bombardment could explain the beam heat load and pressure rise observed for a bunch length of 10 mm

Dagstuhl-Manifest zur Strategischen Bedeutung des Software Engineering in Deutschland

Im Rahmen des Dagstuhl Perspektiven Workshop 05402 "Challenges for Software Engineering Research" haben führende Software Engineering Professoren den derzeitigen Stand der Softwaretechnik in Deutschland charakterisiert und Handlungsempfehlungen für Wirtschaft, Forschung und Politik abgeleitet. Das Manifest fasst die diese Empfehlungen und die Bedeutung und Entwicklung des Fachgebiets prägnant zusammen

Absolute values of the London penetration depth in YBa2Cu3O6+y measured by zero field ESR spectroscopy on Gd doped single crystals

Zero-field electron spin resonance (ESR) of dilute Gd ions substituted for Y in the cuprate superconductor YBa$_2$Cu$_3$O$_{\rm 6+y}$ is used as a novel technique for measuring the absolute value of the low temperature magnetic penetration depth $\lambda(T\to 0)$. The Gd ESR spectrum of samples with $\approx 1$ substitution was obtained with a broadband microwave technique that measures power absorption bolometrically from 0.5 GHz to 21 GHz. This ESR spectrum is determined by the crystal field that lifts the level degeneracy of the spin 7/2 Gd$^{3+}$ ion and details of this spectrum provide information concerning oxygen ordering in the samples. The magnetic penetration depth is obtained by relating the number of Gd ions exposed to the microwave magnetic field to the frequency-integrated intensity of the observed ESR transitions. This technique has allowed us to determine precise values of $\lambda$ for screening currents flowing in the three crystallographic orientations ($\hat a$, $\hat b$ and $\hat c$) in samples of Gd$_{\rm x}$Y$_{\rm 1-x}$Ba$_2$Cu$_3$O$_{6+{\rm y}}$ of three different oxygen contents ${\rm y}=0.993$ ($T_c = 89$ K), ${\rm y}=0.77$ ($T_c=75$ K) and ${\rm y}=0.52$ ($T_c=56$ K). The in-plane values are found to depart substantially from the widely reported relation $T_c\propto 1/\lambda^2$.Comment: 14 pages, 12 figures; version to appear in PR

Phase Separation Models for Cuprate Stripe Arrays

An electronic phase separation model provides a natural explanation for a large variety of experimental results in the cuprates, including evidence for both stripes and larger domains, and a termination of the phase separation in the slightly overdoped regime, when the average hole density equals that on the charged stripes. Several models are presented for charged stripes, showing how density waves, superconductivity, and strong correlations compete with quantum size effects (QSEs) in narrow stripes. The energy bands associated with the charged stripes develop in the middle of the Mott gap, and the splitting of these bands can be understood by considering the QSE on a single ladder.Comment: significant revisions: includes island phase, 16 eps figures, revte

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780

Parkinson’s disease: evolution of cognitive impairment and CSF Aβ₁−₄₂ profiles in a prospective longitudinal study

OBJECTIVE: To evaluate the evolution of cognitive impairment in relation to cerebrospinal fluid (CSF) profiles of amyloid-β (Aβ), total-Tau and phosphorylated-Tau in Parkinson’s disease (PD). METHODS: Prospective, longitudinal, observational study up to 10 years with follow-up every 2  years. We assessed CSF profiles in 415 patients with sporadic PD (median age 66; 63% men) and 142 healthy controls (median age 62; 43% men). RESULTS: Patients with PD with low CSF Aβ₁−₄₂ levels at baseline were more often cognitively impaired than patients with intermediate and high Aβ₁−₄₂ levels. Sixty-seven per cent of the patients with low Aβ₁−₄₂ levels at baseline and normal cognition developed cognitive impairment during follow-up, compared with 41% and 37% of patients having intermediate and high CSF Aβ₁−₄₂ levels. Kaplan-Meier survival curves and Cox regression revealed that patients with low CSF Aβ₁−₄₂ levels at baseline developed cognitive impairment more frequently and earlier during follow-up. CONCLUSION: We conclude that in patients with sporadic PD, low levels of Aβ₁−₄₂ are associated with a higher risk of developing cognitive impairment earlier in the disease process at least in a subgroup of patients