A broad diversity in oxygen affinity to haemoglobin

Oxygen affinity to haemoglobin is indicated by the p50 value (pO2 at 50% O2Hb) and critically determines cellular oxygen availability. Although high Hb-O2 affinity can cause tissue hypoxia under conditions of well O2 saturated blood, individual differences in p50 are commonly not considered in clinical routine. Here, we investigated the diversity in Hb-O2 affinity in the context of physiological relevance. Oxyhaemoglobin dissociation curves (ODCs) of 60 volunteers (18–40 years, both sexes, either endurance trained or untrained) were measured at rest and after maximum exercise (VO2max) test. At rest, p50 values of all participants ranged over 7 mmHg. For comparison, right shift of ODC after VO2max test, representing the maximal physiological range to release oxygen to the tissue, indicated a p50 difference of up to 10 mmHg. P50 at rest differs significantly between women and men, with women showing lower Hb-O2 affinity that is determined by higher 2,3-BPG and BPGM levels. Regular endurance exercise did not alter baseline Hb-O2 affinity. Thus, p50 diversity is already high at baseline level and needs to be considered under conditions of impaired tissue oxygenation. For fast prediction of Hb-O2 affinity by blood gas analysis, only venous but not capillary blood samples can be recommended

Methylated free-circulating HPP1 DNA is an early response marker in patients with metastatic colorectal cancer

Detection of methylated free-circulating DNA (mfcDNA) for hyperplastic polyposis 1 (HPP1) in blood is correlated with a poor prognosis for patients with metastatic colorectal cancers (mCRC). Here, we analyzed the plasma levels of HPP1 mfcDNA in mCRC patients treated with a combination therapy containing a fluoropyrimidine, oxaliplatin and bevacizumab to test whether HPP1 mfcDNA is a suitable prognostic and response biomarker. From 467 patients of the prospective clinical study AIO-KRK-0207, mfcDNA was isolated from plasma samples at different time points and bisulfite-treated mfcDNA was quantified using methylation specific PCR. About 337 of 467 patients had detectable levels for HPP1 mfcDNA before start of treatment. The detection was significantly correlated with poorer overall survival (OS) (HR = 1.86; 95%CI 1.37-2.53). About 2-3 weeks after the first administration of combination chemotherapy, HPP1 mfcDNA was reduced to non-detectable levels in 167 of 337 patients. These patients showed a better OS compared with patients with continued detection of HPP1 mfcDNA (HR HPP1(sample 1: pos/ sample 2: neg) vs. HPP1(neg/neg) = 1.41; 95%CI 1.00-2.01, HPP1(neg,pos/pos) vs. HPP1(neg/neg) = 2.60; 95%CI 1.86-3.64). Receiver operating characteristic analysis demonstrated that HPP1 mfcDNA discriminates well between patients who do (not) respond to therapy according to the radiological staging after 12 or 24 weeks (AUC = 0.77 or 0.71, respectively). Detection of HPP1 mfcDNA can be used as a prognostic marker and an early marker for response (as early as 3-4 weeks after start of treatment compared with radiological staging after 12 or 24 weeks) to identify patients who will likely benefit from a combination chemotherapy with bevacizumab.info:eu-repo/semantics/publishedVersio

Semidefinite Characterization and Computation of Real Radical Ideals

For an ideal $I\subseteq\mathbb{R}[x]$ given by a set of generators, a new semidefinite characterization of its real radical $I(V_\mathbb{R}(I))$ is presented, provided it is zero-dimensional (even if $I$ is not). Moreover we propose an algorithm using numerical linear algebra and semidefinite optimization techniques, to compute all (finitely many) points of the real variety $V_\mathbb{R}(I)$ as well as a set of generators of the real radical ideal. The latter is obtained in the form of a border or Gr\"obner basis. The algorithm is based on moment relaxations and, in contrast to other existing methods, it exploits the real algebraic nature of the problem right from the beginning and avoids the computation of complex components.Comment: 41 page

ISOGAL: A deep survey of the obscured inner Milky Way with ISO at 7 and 15 micron and with DENIS in the near-infrared

The ISOGAL project is an infrared survey of specific regions sampling the Galactic Plane selected to provide information on Galactic structure,stellar populations,stellar mass-loss and the recent star formation history of the inner disk and Bulge of the Galaxy. ISOGAL combines 7 and 15 micron ISOCAM observations - with a resolution of 6'' at worst - with DENIS IJKs data to determine the nature of the sources and theinterstellar extinction. We have observed about 16 square degrees with a sensitivity approaching 10-20mJy, detecting ~10^5 sources,mostly AGB stars,red giants and young stars. The main features of the ISOGAL survey and the observations are summarized in this paper,together with a brief discussion of data processing and quality. The primary ISOGAL products are described briefly (a full description is given in Schuller et al. 2003, astro-ph/0304309): viz. the images and theISOGAL-DENIS five-wavelength point source catalogue. The main scientific results already derived or in progress are summarized. These include astrometrically calibrated 7 and 15um images,determining structures of resolved sources; identification and properties of interstellar dark clouds; quantification of the infrared extinction law and source dereddening; analysis of red giant and (especially) AGB stellar populations in the central Bulge,determining luminosity,presence of circumstellar dust and mass--loss rate,and source classification,supplemented in some cases by ISO/CVF spectroscopy; detection of young stellar objects of diverse types,especially in the inner Bulge with information about the present and recent star formation rate; identification of foreground sources with mid-IR excess. These results are the subject of about 25 refereed papers published or in preparation.Comment: A&A in press. 19 pages,10 Ps figures; problems with figures fixe

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Multi-dimensional modeling and simulation of semiconductor nanophotonic devices

Self-consistent modeling and multi-dimensional simulation of semiconductor nanophotonic devices is an important tool in the development of future integrated light sources and quantum devices. Simulations can guide important technological decisions by revealing performance bottlenecks in new device concepts, contribute to their understanding and help to theoretically explore their optimization potential. The efficient implementation of multi-dimensional numerical simulations for computer-aided design tasks requires sophisticated numerical methods and modeling techniques. We review recent advances in device-scale modeling of quantum dot based single-photon sources and laser diodes by self-consistently coupling the optical Maxwell equations with semiclassical carrier transport models using semi-classical and fully quantum mechanical descriptions of the optically active region, respectively. For the simulation of realistic devices with complex, multi-dimensional geometries, we have developed a novel hp-adaptive finite element approach for the optical Maxwell equations, using mixed meshes adapted to the multi-scale properties of the photonic structures. For electrically driven devices, we introduced novel discretization and parameter-embedding techniques to solve the drift-diffusion system for strongly degenerate semiconductors at cryogenic temperature. Our methodical advances are demonstrated on various applications, including vertical-cavity surface-emitting lasers, grating couplers and single-photon sources

Epilepsy, hippocampal sclerosis and febrile seizures linked by common genetic variation around SCN1A

Epilepsy comprises several syndromes, amongst the most common being mesial temporal lobe epilepsy with hippocampal sclerosis. Seizures in mesial temporal lobe epilepsy with hippocampal sclerosis are typically drug-resistant, and mesial temporal lobe epilepsy with hippocampal sclerosis is frequently associated with important co-morbidities, mandating the search for better understanding and treatment. The cause of mesial temporal lobe epilepsy with hippocampal sclerosis is unknown, but there is an association with childhood febrile seizures. Several rarer epilepsies featuring febrile seizures are caused by mutations in SCN1A, which encodes a brain-expressed sodium channel subunit targeted by many anti-epileptic drugs. We undertook a genome-wide association study in 1018 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 7552 control subjects, with validation in an independent sample set comprising 959 people with mesial temporal lobe epilepsy with hippocampal sclerosis and 3591 control subjects. To dissect out variants related to a history of febrile seizures, we tested cases with mesial temporal lobe epilepsy with hippocampal sclerosis with (overall n = 757) and without (overall n = 803) a history of febrile seizures. Meta-analysis revealed a genome-wide significant association for mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures at the sodium channel gene cluster on chromosome 2q24.3 [rs7587026, within an intron of the SCN1A gene, P = 3.36 × 10−9, odds ratio (A) = 1.42, 95% confidence interval: 1.26-1.59]. In a cohort of 172 individuals with febrile seizures, who did not develop epilepsy during prospective follow-up to age 13 years, and 6456 controls, no association was found for rs7587026 and febrile seizures. These findings suggest SCN1A involvement in a common epilepsy syndrome, give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with febrile seizures, and open avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizure