Solid state NMR of isotope labelled murine fur: a powerful tool to study atomic level keratin structure and treatment effects

We have prepared mouse fur extensively $^{13}$C,$^{15}$N-labelled in all amino acid types enabling application of 2D solid state NMR techniques which establish covalent and spatial proximities within, and in favorable cases between, residues. $^{13}$C double quantum-single quantum correlation and proton driven spin diffusion techniques are particularly useful for resolving certain amino acid types. Unlike 1D experiments on isotopically normal material, the 2D methods allow the chemical shifts of entire spin systems of numerous residue types to be determined, particularly those with one or more distinctively shifted atoms such as Gly, Ser, Thr, Tyr, Phe, Val, Leu, Ile and Pro. Also the partial resolution of the amide signals into two signal envelopes comprising of $\alpha$-helical, and $\beta$-sheet/random coil components, enables resolution of otherwise overlapped $\alpha$-carbon signals into two distinct cross peak families corresponding to these respective secondary structural regions. The increase in resolution conferred by extensive labelling offers new opportunities to study the chemical fate and structural environments of specific atom and amino acid types under the influence of commercial processes, and therapeutic or cosmetic treatments.Medical Research Council (Grant ID: RG75828), Engineering and Physical Sciences Research Council (Ph.D. studentships), National Institute of Health Researc

Preparation of highly and generally enriched mammalian tissues for solid state NMR.

An appreciable level of isotope labelling is essential for future NMR structure elucidation of mammalian biomaterials, which are either poorly expressed, or unexpressable, using micro-organisms. We present a detailed protocol for high level (13)C enrichment even in slow turnover murine biomaterials (fur keratin), using a customized diet supplemented with commercial labelled algal hydrolysate and formulated as a gel to minimize wastage, which female mice consumed during pregnancy and lactation. This procedure produced approximately eightfold higher fur keratin labelling in pups, exposed in utero and throughout life to label, than in adults exposed for the same period, showing both the effectiveness, and necessity, of this approach.The authors would like to acknowledge funding from the Biotechnology and Biological Sciences Research Council for DGR and RR; Engineering and Physical Sciences Research Council for WYC and VWCW; National Institute of Health Research for RAB.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10858-015-9977-

Direct Observation of Proton-Neutron Short-Range Correlation Dominance in Heavy Nuclei

We measured the triple coincidence A(e,e′n p) and A(e,e′ p p) reactions on carbon, aluminum, iron, and lead targets at Q2 \u3e1.5  (GeV/c)2, xB \u3e 1.1 and missing momentum \u3e400  MeV/c. This was the first direct measurement of both proton-proton (pp) and neutron-proton (np) short-range correlated (SRC) pair knockout from heavy asymmetric nuclei. For all measured nuclei, the average proton-proton (pp) to neutron-proton (np) reduced cross-section ratio is about 6%, in agreement with previous indirect measurements. Correcting for single-charge exchange effects decreased the SRC pairs ratio to ∼3%, which is lower than previous results. Comparisons to theoretical generalized contact formalism (GCF) cross-section calculations show good agreement using both phenomenological and chiral nucleon-nucleon potentials, favoring a lower pp to np pair ratio. The ability of the GCF calculation to describe the experimental data using either phenomenological or chiral potentials suggests possible reduction of scale and scheme dependence in cross-section ratios. Our results also support the high-resolution description of high-momentum states being predominantly due to nucleons in SRC pairs

Modified Structure of Protons and Neutrons in Correlated Pairs

The atomic nucleus is made of protons and neutrons (nucleons), that arethemselves composed of quarks and gluons. Understanding how the quark-gluonstructure of a nucleon bound in an atomic nucleus is modified by thesurrounding nucleons is an outstanding challenge. Although evidence for suchmodification, known as the EMC effect, was first observed over 35 years ago,there is still no generally accepted explanation of its cause. Recentobservations suggest that the EMC effect is related to close-proximity ShortRange Correlated (SRC) nucleon pairs in nuclei. Here we report the firstsimultaneous, high-precision, measurements of the EMC effect and SRCabundances. We show that the EMC data can be explained by a universalmodification of the structure of nucleons in neutron-proton (np) SRC pairs andpresent the first data-driven extraction of this universal modificationfunction. This implies that, in heavier nuclei with many more neutrons thanprotons, each proton is more likely than each neutron to belong to an SRC pairand hence to have its quark structure distorted

Diagnostic Classifications and Resource Utilization of Decedents Served by the Department of Veterans Affairs

Background: Given the volume and cost of inpatient care during the last year of life, there is a critical need to identify patterns of dying as a means of planning end-of-life care services, especially for the growing number of older persons who receive services from the Veterans Health Administration (VHA). Methods: A retrospective computerized record review was conducted of 20,933 VHA patients who died as inpatients between October 1, 2001 and September 30, 2002. Diagnoses were aggregated into one of five classification patterns of death and analyzed in terms of health care resource utilization (mean number of inpatient days and cumulative outpatient visits in the year preceding the patient's death). Results: Cancer deaths were the most common (30.4%) followed by end-stage renal disease (ESRD) (23.2%), cardiopulmonary failure (21.4%), frailty (11.6%), “other” diagnoses (7.3%), and sudden deaths (6.1%). Those with ESRD were more likely to be male and nonwhite (p < 0.05) and those with frailty were more likely to be older and married (p < 0.05). Controlling for demographic variables, those with frailty had the highest number of inpatient days while those with ESRD had the highest number of outpatient visits. Nonmarried status was associated with more inpatient days, especially among younger decedents. Conclusion: As a recognized leader in end-of-life care, the VHA can play a unique role in the development of specific interventions that address the diverse needs of persons with different dying trajectories identified through this research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63159/1/jpm.2006.0256.pd

Probing High-Momentum Protons and Neutrons in Neutron-Rich Nuclei

The atomic nucleus is one of the densest and most complex quantum-mechanical systems in nature. Nuclei account for nearly all the mass of the visible Universe. The properties of individual nucleons (protons and neutrons) in nuclei can be probed by scattering a high-energy particle from the nucleus and detecting this particle after it scatters, often also detecting an additional knocked-out proton. Analysis of electron- and proton-scattering experiments suggests that some nucleons in nuclei form close-proximity neutron–proton pairs with high nucleon momentum, greater than the nuclear Fermi momentum. However, how excess neutrons in neutron-rich nuclei form such close-proximity pairs remains unclear. Here we measure protons and, for the first time, neutrons knocked out of medium-to-heavy nuclei by high-energy electrons and show that the fraction of high-momentum protons increases markedly with the neutron excess in the nucleus, whereas the fraction of high-momentum neutrons decreases slightly. This effect is surprising because in the classical nuclear shell model, protons and neutrons obey Fermi statistics, have little correlation and mostly fill independent energy shells. These high-momentum nucleons in neutron-rich nuclei are important for understanding nuclear parton distribution functions (the partial momentum distribution of the constituents of the nucleon) and changes in the quark distributions of nucleons bound in nuclei (the EMC effect). They are also relevant for the interpretation of neutrino-oscillation measurements and understanding of neutron-rich systems such as neutron stars

Scheme for the generation of an entangled four-photon W-state

We present a scheme to produce an entangled four-photon W-state by using linear optical elements. The symmetrical setup of linear optical elements consists of four beam splitters, four polarization beam splitters and four mirrors. A photon EPR-pair and two single photons are required as the input modes. The projection on the W-state can be made by a four-photon coincidence measurement. Further, we show that by means of a horizontally oriented polarizer in front of one detector the W-state of three photons can be generated.Comment: titile is changed, to appear in PR