Strong Differential Photoion Circular Dichroism in Strong-Field Ionization of Chiral Molecules.

We investigate the differential ionization probability of chiral molecules in the strong-field regime as a function of the helicity of the incident light. To this end, we analyze the fourfold ionization of bromochlorofluoromethane (CHBrClF) with subsequent fragmentation into four charged fragments and different dissociation channels of the singly ionized methyloxirane. By resolving for the molecular orientation, we show that the photoion circular dichroism signal strength is increased by 2 orders of magnitude.

Menthol stimulates calcium absorption in the rumen but not in the jejunum of sheep.

Stimulation of Ca2+ absorption can counteract hypocalcemia at the onset of lactation. The plant bioactive lipid compound (PBLC) menthol is an agonist for nonselective cation channels of the transient receptor potential (TRP) family. It acutely stimulated Ca2+ absorption in ruminal epithelia of nonadapted animals ex vivo and caused higher plasma Ca2+ concentrations in cows and sheep in vivo. To elucidate the pathway by which menthol feeding increases plasma Ca2+ level, the present study aimed to investigate the long-term dose-dependent effects of dietary menthol-rich PBLC on Ca2+ absorption and mRNA abundances of TRP channels in both rumen and jejunum. Twenty-four growing Suffolk sheep were equally distributed to a Con, PBLC-L, and PBLC-H group, which received 0, 80, and 160 mg/d of a menthol-rich PBLC. After 4 wk, ruminal and jejunal epithelia were analyzed for mRNA abundances of TRPA1, TRPV3, TRPV5-6, and TRPM6-8 genes. The Ca2+ flux rates and electrophysiological properties of epithelia from rumen and mid-jejunum were measured in Ussing chambers in the presence and absence of mucosal Na+. Acute changes in Ca2+ flux rates were measured after mucosal application of 50 µM menthol. Ruminal epithelia had quantifiable transcripts of TRPV3 = TRPM6 >TRPM7 >TRPA1 with no difference among feeding groups. Jejunum had quantifiable transcripts of TRPM7 >TRPA1 ≥ TRPM6 ≥ TRPV6 >TRPV5, where TRPA1, TRPV5, and TRPV6 tended to decrease linearly with increasing PBLC dose. Absorptive net flux of Ca2+ was detected only in the rumen, whereas jejunum showed a high passive permeability to Ca2+. Net flux rates of Ca2+ in the rumen increased in a quadratic manner (highest in PBLC-L animals) and were systematically decreased with the omission of mucosal Na+. Short-circuit current increased in both PBLC feeding groups compared with Con only in the rumen. Acute application of menthol-stimulated mucosal-to-serosal and net Ca2+ flux rates only in ruminal epithelia with higher stimulation in PBLC-fed animals. We conclude that Ca2+ transport is mainly active and transcellular in the rumen. It most likely involves TRPV3 that can be stimulated by menthol. Pre-feeding of menthol-rich PBLC enhances ruminal Ca2+ absorption and sensitizes it to acute stimulation by menthol. By contrast, intestinal Ca2+ absorption is not sensitive to menthol stimulation. Menthol could be used as a tool to enhance ruminal Ca2+ absorption and to prevent hypocalcemia in dairy cows.

Tracking the adoption of bread wheat varieties in Afghanistan using DNA fingerprinting.

BACKGROUND: Wheat is the most important staple crop in Afghanistan and accounts for the main part of cereal production. However, wheat production has been unstable during the last decades and the country depends on seed imports. Wheat research in Afghanistan has emphasized releases of new, high-yielding and disease resistant varieties but rates of adoption of improved varieties are uncertain. We applied DNA fingerprinting to assess wheat varieties grown in farmers' fields in four Afghan provinces. RESULTS: Of 560 samples collected from farmers' fields during the 2015-16 cropping season, 74% were identified as varieties released after 2000, which was more than the number reported by farmers and indicates the general prevalence of use of improved varieties, albeit unknowingly. At the same time, we found that local varieties and landraces have been replaced and were grown by 4% fewer farmers than previously reported. In 309 cases (58.5%), farmers correctly identified the variety they were growing, while in 219 cases (41.5%) farmers did not. We also established a reference library of released varieties, elite breeding lines, and Afghan landraces, which confirms the greater genetic diversity of the landraces and their potential importance as a genetic resource. CONCLUSIONS: Our study is the first in wheat to apply DNA fingerprinting at scale for an accurate assessment of wheat varietal adoption and our findings point up the importance of DNA fingerprinting for accuracy in varietal adoption studies.

Justifying Nonstandard Exception Requests for Pediatric Liver Transplant Candidates: An Analysis of Narratives Submitted to the United Network for Organ Sharing, 2009-2014.

Nonstandard exception requests (NSERs), for which transplant centers provide patient-specific narratives to support a higher Model for End-stage Liver Disease/Pediatric End-stage Liver Disease score, are made for >30% of pediatric liver transplant candidates. We describe the justifications used in pediatric NSER narratives 2009-2014 and identify justifications associated with NSER denial, waitlist mortality, and transplant. Using United Network for Organ Sharing data, 1272 NSER narratives from 1138 children with NSERs were coded for analysis. The most common NSER justifications were failure-to-thrive (48%) and risk of death (40%); both associated with approval. Varices, involvement of another organ, impaired quality of life, and encephalopathy were justifications used more often in denied NSERs. Of the 25 most prevalent justifications, 60% were not associated with approval or denial. Waitlist mortality risk was increased when fluid overload or "posttransplant complication outside standard criteria" were cited and decreased when liver-related infection was noted. Transplant probability was increased when the narrative mentioned liver-related infections, and fluid overload for children <2 years old; it decreased when "posttransplant complications outside standard criteria" and primary sclerosing cholangitis were cited. This analysis provides novel insight and suggests targets for future consideration in outcomes research and exception criteria. Changes in the allocation system are needed to ensure equity and optimize outcomes for all pediatric candidates.

Nonstandard Exception Requests Impact Outcomes for Pediatric Liver Transplant Candidates.

Nonstandard exceptions requests (NSERs), in which transplant centers appeal on a case-by-case basis for Pediatric End-Stage Liver Disease/Mayo End-Stage Liver Disease points, have been highly utilized for pediatric liver transplant candidates. We evaluated whether NSE outcomes are associated with waitlist and posttransplant mortality. United Network for Organ Sharing (UNOS) Scientific Registry of Transplant Recipients data on pediatric liver transplant candidates listed in 2009-2014 were analyzed after excluding those granted automatic UNOS exceptions. Of 2581 pediatric waitlist candidates, 44% had an NSE request. Of the 1134 children with NSERs, 93% were approved and 7% were denied. For children 2-18 years at listing, NSER denial increased the risk of waitlist mortality or removal for being too sick (subhazard ratio 2.99, 95% confidence interval [CI] 1.26-7.07, p = 0.01 in multivariate analysis). For children younger than 2 years, NSER denial did not impact waitlist mortality/removal. Children with NSER approved had reduced risk of graft loss 3 years posttransplant in univariate but not multivariable analysis (odds ratio 0.73, 95% CI 0.53-1.01, p = 06). Those with NSER denial had a higher risk of posttransplant death than those with no NSER (hazard ratio 2.43, 95% CI 0.99-5.95, p = 0.05, multivariable analysis), but NSER approval did not impact posttransplant death. Further research on NSER utilization in pediatric liver transplant is needed to optimize organ allocation and outcomes for children.

Skyrmion-Based Dynamic Magnonic Crystal.

A linear array of periodically spaced and individually controllable skyrmions is introduced as a magnonic crystal. It is numerically demonstrated that skyrmion nucleation and annihilation can be accurately controlled by a nanosecond spin polarized current pulse through a nanocontact. Arranged in a periodic array, such nanocontacts allow the creation of a skyrmion lattice that causes a periodic modulation of the waveguide's magnetization, which can be dynamically controlled by changing either the strength of an applied external magnetic field or the density of the injected spin current through the nanocontacts. The skyrmion diameter is highly dependent on both the applied field and the injected current. This implies tunability of the lowest band gap as the skyrmion diameter directly affects the strength of the pinning potential. The calculated magnonic spectra thus exhibit tunable allowed frequency bands and forbidden frequency bandgaps analogous to that of conventional magnonic crystals where, in contrast, the periodicity is structurally induced and static. In the dynamic magnetic crystal studied here, it is possible to dynamically turn on and off the artificial periodic structure, which allows switching between full rejection and full transmission of spin waves in the waveguide. These findings should stimulate further research activities on multiple functionalities offered by magnonic crystals based on periodic skyrmion lattices.

High uterosacral vault suspension vs Sacrocolpopexy for treating apical defects: a randomized controlled trial with twelve months follow-up.

INTRODUCTION AND HYPOTHESIS: The high uterosacral vault suspension (HUVS) is a vaginal approach for treating apical prolapse that provides shorter operative and recovery times and is associated with lower morbidity rates. Success rates reported for this technique are comparable with the abdominal sacrocolpopexy (SCP); however, to date, there are no prospective randomized studies comparing HUVS to SCP. The aim of the study was to compare the anatomical objective cure rates for the apical compartment in patients undergoing either HUVS or SCP at 12 months' follow-up. METHODS: We performed a single-center parallel randomized controlled trial in patients with severe apical defect defined as Pelvic Organ Prolapse Quantification (POP-Q) point C ≥ stage 3. Based on the center's previous experience, a sample size of 124 patients was required to show a 20% cure rate difference between both techniques with 80% power and using a two-tailed 5% level of significance. One hundred and ten patients were available for analysis; 54 were allocated to abdominal SCP and 56 to HUVS. The primary outcome was to evaluate surgical objective success defined as POP-Q point C stage<2. The Pelvic Floor Distress Inventory (PFDI-20), the Perceived Quality of Life Scale (P-QOL), and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) questionnaires were used for subjective assessment. RESULTS: The objective success rate for apical suspension at 12 months' follow-up was 100% for abdominal SCP and 82.5% for HUVS (log-rank p 0.033). Both techniques showed a significant improvement with regards to prolapse symptoms, quality of life (QOL), and sexual function. The significant improvement in postoperative questionnaires was comparable between both surgeries at 12 months' follow-up. CONCLUSIONS: Abdominal SCP has statistically significant better anatomical results when compared with HUVS for correcting apical defects at 12 months.

A minimal physiologically based model of the HPA axis under influence of the sleep-wake cycles.

The hypothalamic-pituitary-adrenal axis (also called the HPA or stress axis) exhibits distinct circadian and ultradian rhythms in cortisol release that cannot be explained solely by the feedback loops from cortisol to the control systems in the paraventricular nucleus (PVN) and pituitary gland. The HPA axis is intimately connected with other brain functions. In particular, it is strongly affected by the sleep-wake cycles via direct and indirect effects of the circadian and homeostatic mechanisms. For example, the HPA axis has direct inputs from the master circadian clock in the suprachiasmatic nuclei (SCN), and from the various sleep-wake related neuronal populations, which themselves are under the effects of the circadian and homeostatic processes. In this paper a first step towards a physiologically based mathematical model of the HPA-axis under effects of the sleep-wake cycles is presented. This model accounts for 3 major characteristics of daily cortisol profile in the blood: i) abrupt increase of cortisol concentration in response to awakening, the so-called cortisol-awakening response (CAR); ii) reduced cortisol levels during daytime with underlying ultradian oscillations; and iii) suppression of cortisol release during sleep.

Human dietary δ(15)N intake: representative data for principle food items.

Dietary analysis using δ(15)N values of human remains such as bone and hair is usually based on general principles and limited data sets. Even for modern humans, the direct ascertainment of dietary δ(15)N is difficult and laborious, due to the complexity of metabolism and nitrogen fractionation, differing dietary habits and variation of δ(15)N values of food items. The objective of this study was to summarize contemporary regional experimental and global literature data to ascertain mean representative δ(15)N values for distinct food categories. A comprehensive data set of more than 12,000 analyzed food samples was summarized from the literature. Data originated from studies dealing with (1) authenticity tracing or origin control of food items, and (2) effects of fertilization or nutrition on δ(15)N values of plants or animals. Regional German food δ(15)N values revealed no major differences compared with the mean global values derived from the literature. We found that, in contrast to other food categories, historical faunal remains of pig and poultry are significantly enriched in (15)N compared to modern samples. This difference may be due to modern industrialized breeding practices. In some food categories variations in agricultural and feeding regimens cause significant differences in δ(15)N values that may lead to misinterpretations when only limited information is available.

Feasibility of balloon sinuplasty in patients with chronic rhinosinusitis: the Graz experience.

BACKGROUND: Balloon sinuplasty (BSP) is a catheter-based technique to dilate sinus ostia and drainage pathways to create ventilation and drainage. The aim of this study was to evaluate the feasibility of BSP in routine treatment of patients suffering from chronic rhinosinusitis (CRS). METHODOLOGY: Patients with CRS refractory to medical therapy who had been scheduled for endoscopic sinus surgery between 2009 and 2011 were included in this study. RESULTS: Forty-five consecutive patients were included in this study, in whom 112 sinuses were approached by BSP. Of the 112 sinuses, 68 (60%) were planned as a "Balloon-Only" procedure and 44 (40%) were planned as a "Hybrid" procedure. Of the 68 sinuses in the "Balloon-Only" group, in 44 sinuses BSP failed, equating to a failure rate of 65%. Forty-four sinuses were planned for "Hybrid" procedures. In 29 of these sinuses BSP failed, giving a failure rate of 66%. CONCLUSION: According to literature, BSP can be a useful adjunct technique to standard FESS. In our experience, however, a failure rate of 65% for "Balloon-Only" and of 66% for "Hybrid" procedures occurred, which was regarded as unacceptable by the study group. Therefore, the study initially scheduled for 200 consecutive patients, was abandoned.

Heterozygous mutations in ANKH, the human ortholog of the mouse progressive ankylosis gene, result in craniometaphyseal dysplasia.

Craniometaphyseal dysplasia (CMD) is a bone dysplasia characterized by overgrowth and sclerosis of the craniofacial bones and abnormal modeling of the metaphyses of the tubular bones. Hyperostosis and sclerosis of the skull may lead to cranial nerve compressions resulting in hearing loss and facial palsy. An autosomal dominant form of the disorder (MIM 123000) was linked to chromosome 5p15.2-p14.1 (ref. 3) within a region harboring the human homolog (ANKH) of the mouse progressive ankylosis (ank) gene. The ANK protein spans the outer cell membrane and shuttles inorganic pyrophosphate (PPi), a major inhibitor of physiologic and pathologic calcification, bone mineralization and bone resorption. Here we carry out mutation analysis of ANKH, revealing six different mutations in eight of nine families. The mutations predict single amino acid substitutions, deletions or insertions. Using a helix prediction program, we propose for the ANK molecule 12 membrane-spanning helices with an alternate inside/out orientation and a central channel permitting the passage of PPi. The mutations occur at highly conserved amino acid residues presumed to be located in the cytosolic portion of the protein. Our results link the PPi channel ANK with bone formation and remodeling.

Cholesterol granulomas of the petrous apex; endonasal endoscopic approach.

OBJECTIVE: Cholesterol granulomas are benign lesions that sometimes occur on the petrous apex (PA). We report our experience using an endoscopic endonasal approach to remove PA cholesterol granulomas. MATERIAL AND METHODS: A retrospective patient chart analysis was conducted at a tertiary care university hospital. RESULTS: Four patients (3 females, 1 male) were included in this study. Patients' ages ranged from 27 to 78 years. Computed tomography (CT) and magnetic resonance imaging (MRI) for diagnosis and computer-assisted navigation were performed. The most common symptom was abducens nerve palsy. The largest granuloma measured 5 x 2 cm and was located on the left side. An endoscopic endonasal approach was chosen and navigation was applied (3/4 patients) to identify the optimal area for opening the granuloma. No complications occurred, and patients were free from recurrence during the follow-up period. CONCLUSION: The endoscopic endonasal approach to PA cholesterol granulomas is feasible and safe. Intra-operative navigation is recommended to identify the position of the internal carotid artery and determine the safest area for opening the granuloma without damaging the artery. Another advantage of this approach is an easier follow-up through diagnostic nasal endoscopy.

An insight into what superconducts in polycrystalline boron-doped diamonds based on investigations of microstructure.

The discovery of superconductivity in polycrystalline boron-doped diamond (BDD) synthesized under high pressure and high temperatures [Ekimov, et al. (2004) Nature 428:542-545] has raised a number of questions on the origin of the superconducting state. It was suggested that the heavy boron doping of diamond eventually leads to superconductivity. To justify such statements more detailed information on the microstructure of the composite materials and on the exact boron content in the diamond grains is needed. For that we used high-resolution transmission electron microscopy and electron energy loss spectroscopy. For the studied superconducting BDD samples synthesized at high pressures and high temperatures the diamond grain sizes are approximately 1-2 mum with a boron content between 0.2 (2) and 0.5 (1) at %. The grains are separated by 10- to 20-nm-thick layers and triangular-shaped pockets of predominantly (at least 95 at %) amorphous boron. These results render superconductivity caused by the heavy boron doping in diamond highly unlikely.

Self-referencing circular dichroism ion yield measurements for improved statistics using femtosecond laser pulses.

The combination of circular dichroism with laser mass spectrometry via the measurement of ion yields is a powerful tool in chiral recognition, but the measured anisotropies are generally weak. The method presented in this contribution reduces the measurement error significantly. A common path optical setup generates a pair of counter-rotating laser foci in the interaction region of a time-of-flight spectrometer. As the space focus condition is fulfilled for both foci individually, this becomes a twin-peak ion source with well separated and sufficiently resolved mass peaks. The individual control of polarization allows for in situ correction of experimental fluctuations measuring circular dichroism. Our robust optical setup produces reliable and reproducible results and is applicable for dispersion sensitive femtosecond laser pulses. In this contribution, we use 3-methyl-cyclopentanone as a prototype molecule to illustrate the evaluation procedure and the measurement principle.

Experimental demonstration of novel beam characterization using a polarizable X-band transverse deflection structure.

The PolariX TDS (Polarizable X-Band Transverse Deflection Structure) is an innovative TDS-design operating in the X-band frequency-range. The design gives full control of the streaking plane, which can be tuned in order to characterize the projections of the beam distribution onto arbitrary transverse axes. This novel feature opens up new opportunities for detailed characterization of the electron beam. In this paper we present first measurements of the Polarix TDS at the FLASHForward beamline at DESY, including three-dimensional reconstruction of the charge-density distribution of the bunch and slice emittance measurements in both transverse directions. The experimental results open the path toward novel and more extensive beam characterization in the direction of multi-dimensional-beam-phase-space reconstruction.

Intrinsic emittance reduction of an electron beam from metal photocathodes.

Electron beams in modern linear accelerators are now becoming limited in brightness by the intrinsic emittance of the photocathode electron source. Therefore it becomes important for large scale facilities such as free electron lasers to reduce this fundamental limit. In this Letter we present measurements of the intrinsic emittance for different laser wavelength (from 261 to 282 nm) and for different photocathode materials such as Mo, Nb, Al, Cu. Values as low as 0.41±0.03 mm·mrad/mm laser spot size (rms) were measured for a copper photocathode illuminated with a 282 nm laser wavelength. The key element for emittance reduction is a uv laser system which allows adjustment of the laser photon energy to match the effective work function of the cathode material and to emit photoelectrons with a lower initial kinetic energy. The quantum efficiency over the explored wavelength range varies by less than a factor of 3.

Neurones and synapses for systemic models of psychiatric disorders.

We propose a mechanism-based modelling approach which brings together the most relevant features of neural dynamics and synaptic transmission for clinically valuable simulations of psychiatric disorders and their pharmaceutical treatment. It is based on a minimal, but physiologically justified concept, which allows to account for a great diversity of neuronal dynamics and synaptic mechanisms. It can simulate ionotropic as well as metabotropic receptors in addition to the effects of eventual co-transmitters and external neuromodulators. The proposed model can mimic the clinically most important aspects of synaptic disturbances, such as impaired transmitter availability or reduced number of postsynaptic receptors, for example due to their internalization as a function of transmitter concentration. It also allows evaluation of the effects of drugs with specific actions such as receptor agonists and antagonists or reuptake inhibitors. It is a major advantage of this physiologically based approach that it can be adjusted to different types of neurons and synapses, and also can be extended to more elaborate physiological situations, e. g. by including additional receptors or ion channels, whenever this is indicated by clinical or experimental data.

Effects of donor age and cell senescence on kidney allograft survival.

The biological processes responsible for somatic cell senescence contribute to organ aging and progression of chronic diseases, and this may contribute to kidney transplant outcomes. We examined the effect of pre-existing donor aging on the performance of kidney transplants, comparing mouse kidney isografts and allografts from old versus young donors. Before transplantation, old kidneys were histologically normal, but displayed an increased expression of senescence marker p16(INK4a). Old allografts at day 7 showed a more rapid emergence of epithelial changes and a further increase in the expression of p16(INK4a). Similar but much milder changes occurred in old isografts. These changes were absent in young allografts at day 7, but emerged by day 21. The expression of p16(INK4a) remained low in young kidney allografts at day 7, but increased with severe rejection at day 21. Isografts from young donors showed no epithelial changes and no increase in p16(INK4a). The measurements of the alloimmune response-infiltrate, cytology, expression of perforin, granzyme B, IFN-gamma and MHC-were not increased in old allografts. Thus, old donor kidneys display abnormal parenchymal susceptibility to transplant stresses and enhanced induction of senescence marker p16(INK4a), but were not more immunogenic. These data are compatible with a key role of somatic cell senescence mechanisms in kidney transplant outcomes by contributing to donor aging, being accelerated by transplant stresses, and imposing limits on the capacity of the tissue to proliferate.

Effect of chemical composition on superconductivity and magnetism in layered ruthenocuprates.

The ruthenium-based layered cuprates RuSr(2)GdCu(2)O(8) (RuGd1212) can be considered naturally occurring magnetic and superconducting multilayer systems. We have concentrated on the preparation of RuGd1212-type compounds with nominally stoichiometric composition under ambient pressure conditions. For small rare earth ions R  = Gd, Eu (and Sm), single phase compounds are obtained with the typical ordered layered structure and no significant changes of physical properties. With large rare earth ions (R  = Nd, Pr), multiphase samples are obtained. In these cases, no ordered layered structure was observed. The effect of substituting Sr(2+) with the smaller Ca(2+) and larger Ba(2+) is examined. A different number and different types of phases in equilibrium are found with different alkaline earths (A  = Ca, Sr, Ba) at the nominal RuA(2)NdCu(2)O(8) composition. The variation in the mismatch of the A/Nd size does not lead to the formation of an ordered layered RuA(2)NdCu(2)O(8) compound. Chemical transport in an open system was used to vary the Ru content in the RuGd1212 samples during the annealing step. With an increase of the Ru mass transport to the sample, the composition can be driven beyond the limit of the homogeneity range. Systematic changes in the phase composition of the resulting sample were observed. The magnetic and superconducting transition temperatures vary in a systematic way and are attributed to a variation of the Ru content in the RuR1212 phase.

Electronic band effects on the spin disorder resistivity of Gd(4)(Co(1-x)Cu(x))(3) compounds.

We present a study of the spin disorder resistivity ([Formula: see text]) and the electronic specific heat coefficient (γ) in Gd(4)(Co(1-x)Cu(x))(3) compounds, with x = 0.00, 0.05, 0.10, 0.20 and 0.30. The experimental results show a strongly nonlinear dependence of [Formula: see text] on the average de Gennes factor (G(av)) which, in similar intermetallic compounds, is usually attributed to the existence of spin fluctuations on the Co 3d bands. Values of γ were found around 110 mJ mol(-1) K(-2) for the Gd(4)(Co(1-x)Cu(x))(3) compounds, much larger than 38.4 mJ mol(-1) K(-2) found for the isostructural nonmagnetic Y(4)Co(3) compound. Using a novel type of analysis we show that the ratio [Formula: see text] follows a well-defined linear dependence on G(av), which is expected when appropriate dependencies with the effective electron mass are taken into account. This indicates that band structure effects, rather than spin fluctuations, could be the main cause for the strong electron scattering and γ enhancement observed in the Gd(4)(Co(1-x)Cu(x))(3) compounds. A discussion on relevant features of magnetization and electrical resistivity data, for the same series of compounds, is also presented.