Signatures of Interactions in the Andreev Spectrum of Nanowire Josephson Junctions.

We performed microwave spectroscopy of an InAs nanowire between superconducting contacts implementing a finite-length, multichannel Josephson weak link. Certain features in the spectra, such as the splitting by spin-orbit interactions of the transition lines among Andreev states, have been already understood in terms of noninteracting models. However, we identify here additional transitions, which evidence the presence of Coulomb interactions. By combining experimental measurements and model calculations, we reach a qualitative understanding of these very rich Andreev spectra.

From Adiabatic to Dispersive Readout of Quantum Circuits.

Spectral properties of a quantum circuit are efficiently read out by monitoring the resonance frequency shift it induces in a microwave resonator coupled to it. When the two systems are strongly detuned, theory attributes the shift to an effective resonator capacitance or inductance that depends on the quantum circuit state. At small detuning, the shift arises from the exchange of virtual photons, as described by the Jaynes-Cummings model. Here we present a theory bridging these two limits and illustrate, with several examples, its necessity for a general description of quantum circuits readout.

Incorporating the patient perspective in the study of rare bone disease: insights from the osteogenesis imperfecta community.

There is limited research which examines health concerns of individuals with osteogenesis imperfecta (OI). Discussion groups with leaders of the adult OI community identified a broad range of medical priorities beyond fractures and brittle bones. Our work underscores the need to include patient-reported outcomes in rare bone disease research. INTRODUCTION: Osteogenesis imperfecta (OI) is a rare genetic disorder affecting collagen protein leading to brittle bones and a number of other medical complications. To date, there is limited research which examines the life-long process of aging with this rare disease, much less the perspective of individuals with OI. METHODS: In order to explore and prioritize health concerns that adults with OI feel have been inadequately addressed in health care and research, investigators held discussions with leaders from the global adult OI community. The meetings were held in August 2017 at the 13th International Conference on OI in Oslo, Norway as part of the preconference seminar "Patient Participation in OI Research". Investigators were part of the Brittle Bone Disease Consortium (BBDC), a multicenter research program devoted to the study of OI, and their focus was on patient-reported outcomes (PRO). RESULTS: Participants noted that while fractures and brittle bones are the most common feature of OI, a number of body systems are under-studied in this disorder. They particularly emphasized breathing, hearing, and the effects of aging as primary concerns that researchers and physicians may not fully understand or address. Other areas included pain, gastrointestinal problems, mental health, nutrition, menopause/pregnancy, and basilar invagination. Participants also emphasized that they must be informed of study results. They underscored that outcome measures incorporated into future drug trials must look beyond fractures and consider the whole patient. CONCLUSIONS: This work will help guide the incorporation of PROs into the next phase of the BBDC Natural History Study of OI and underscores the importance of including PROs in the study of rare diseases.

The American Orthopaedic Association's Own the Bone® database: a national quality improvement project for the treatment of bone health in fragility fracture patients.

The American Orthopaedic Association initiated the Own the Bone (OTB) quality improvement program in 2009. Herein we show that the data collected through this program is similar to that collected in other large studies. Thus, the OTB registry functions as an externally valid cohort for studying fragility fracture patients. INTRODUCTION: The American Orthopedic Association initiated the Own the Bone (OTB) quality improvement program in 2009 to improve secondary prevention of fragility fractures. In this study, we present a summary of the data collected by the OTB program and compare it to data from other large fragility fracture registries with an aim to externally validate the OTB registry. METHODS: The OTB registry contained 35,038 unique cases of fragility fracture as of September, 2016. We report the demographics, presenting fracture characteristics, past fracture history, and bone mineral density (BMD) data and compare these to data from large fragility fracture studies across the world. RESULTS: Seventy-three percent of the patients in the OTB registry were female, Caucasian, and post-menopausal. In 54.4% of cases, patients had a hip fracture; spine fractures were the second most common fracture type occurring in 11.1% of patients. Thirty-four percent of the patients had a past history of fragility fracture, and the most common sites were the spine and hip. The average femoral neck T-score was - 2.06. When compared to other studies, the OTB database showed similar findings with regard to patient age, gender, race, BMI, BMD profile, prior fracture history, and family history of fragility fractures. CONCLUSION: OTB is the first and largest multi-center voluntary fragility fracture registry in the USA. The data collected through the OTB program is comparable to that collected in international studies. Thus, the OTB registry functions as an externally valid cohort for further studies assessing the clinical characteristics, interventions, and outcomes achieved in patients who present with a fragility fracture in the USA.

Cutaneous skeletal hypophosphatemia syndrome: clinical spectrum, natural history, and treatment.

Cutaneous skeletal hypophosphatemia syndrome (CSHS), caused by somatic RAS mutations, features excess fibroblast growth factor-23 (FGF23) and skeletal dysplasia. Records from 56 individuals were reviewed and demonstrated fractures, scoliosis, and non-congenital hypophosphatemia that in some cases were resolved. Phosphate and calcitriol, but not skin lesion removal, were effective at controlling hypophosphatemia. No skeletal malignancies were found. PURPOSE: CSHS is a disorder defined by the association of epidermal and/or melanocytic nevi, a mosaic skeletal dysplasia, and an FGF23-mediated hypophosphatemia. To date, somatic RAS mutations have been identified in all patients whose affected tissue has undergone DNA sequencing. However, the clinical spectrum and treatment are poorly defined in CSHS. The purpose of this study is to determine the spectrum of the phenotype, natural history of the disease, and response to treatment of hypophosphatemia. METHODS: Five CSHS subjects underwent prospective data collection at clinical research centers. A review of the literature identified 45 reports that included a total of 51 additional patients, in whom the findings were compatible with CSHS. Data on nevi subtypes, bone histology, mineral and skeletal disorders, abnormalities in other tissues, and response to treatment of hypophosphatemia were analyzed. RESULTS: Fractures, limb deformities, and scoliosis affected most CSHS subjects. Hypophosphatemia was not present at birth. Histology revealed severe osteomalacia but no other abnormalities. Skeletal dysplasia was reported in all anatomical compartments, though less frequently in the spine; there was no clear correlation between the location of nevi and the skeletal lesions. Phosphate and calcitriol supplementation was the most effective therapy for rickets. Convincing data that nevi removal improved blood phosphate levels was lacking. An age-dependent improvement in mineral abnormalities was observed. A spectrum of extra-osseous/extra-cutaneous manifestations that included both benign and malignant neoplasms was present in many subjects, though osteosarcoma remains unreported. CONCLUSION: An understanding of the spectrum, natural history, and efficacy of treatment of hypophosphatemia in CSHS may improve the care of these patients.

The effect of gender and gender match on mortality in pediatric heart transplantation.

The effect of organ-recipient gender match on pediatric heart transplant mortality is unknown. We analyzed the effects of gender and donor-recipient gender matching. Based on Organ Procurement and Transplant Network data, we performed a historical cohort study in a population of 3630 heart transplant recipients less than 18 years old. We compared unadjusted and adjusted mortality by recipient gender, donor gender and between gender-matched and gender-mismatched recipients. Female recipients had decreased survival compared to male recipients (unadjusted hazard ratio [HR] 1.16, confidence interval [CI] 1.02-1.31; p = 0.020). Organ-recipient gender mismatch did not affect mortality for either male or female recipients, though gender-mismatched females had the worst survival compared to gender-matched males, who had the best survival (unadjusted HR 1.26, CI 1.07-1.49; p = 0.005). After adjustment for other risk factors affecting transplant mortality, female recipients had decreased survival compared to male recipients (HR 1.27, CI 1.12-1.44; p = 0.020) and gender matching had no effect. In conclusion, gender mismatch alone did not increase long-term mortality for pediatric heart transplant recipients. However, there may be additive effects of gender and gender matching affecting survival. There are insufficient data at this time to support that recipient and donor gender should affect heart allocation in children.

Resolving the thickness of peat deposits with contact-less electromagnetic methods: A case study in the Venice coastland.

Peat soils are typical deposits characterizing wetlands and reclaimed farmlands. They are important carbon reservoirs and when degraded (e.g., erosive processes, fires, draining and plowing) massive carbon dioxide volumes are released. This leads to increase greenhouse effect and induce serious land subsidence. Thus, mapping the volume of peat deposits is crucial in order to estimate the carbon mass and the potential release of carbon dioxide and consequent loss in soil elevation. Despite the importance of such estimations, forecasting and quantifying the peat thickness is still a challenge. Direct sediment coring provides local information that is difficult to extend to large territories. Indirect geophysical methods are unable to resolve lithological contrasts in the presence of saltwater contamination in coastal areas. In this work, we show the results obtained using two contact-less electromagnetic methods for the characterization of peat deposits in a peatland site of the Venice coastland, Italy. Specifically, a multi-frequency portable instrument (FDEM) and an airborne time-domain electromagnetic one (AEM), known for their very high and relatively low vertical resolution respectively, were used to collect data over a former wetland then reclaimed for agricultural purposes. Additional electrical resistivity tomography (ERT) data are used together with sediment core data to assess the effectiveness and accuracy of the contact-less methods. Results show that both FDEM and AEM are very effective in detecting the presence of the peat layer, despite its low thickness (<2 m) and the high electro-conductive subsoil because of saltwater contamination. However, the AEM method overestimated the peat thickness while the FDEM could accurately resolve the peat thickness even where the layer was thinner than 1 m. When compared to the electrical features extracted from the ERT, discrepancies are on average lower than 30%; when compared to the borehole data, discrepancies are on average slightly higher than 6%.

Destructive quantum interference in transport through molecules with electron-electron and electron-vibration interactions.

We study the transport through a molecular junction exhibiting interference effects. We show that these effects can still be observed in the presence of molecular vibrations if Coulomb repulsion is taken into account. In the Kondo regime, the conductance of the junction can be changed by several orders of magnitude by tuning the levels of the molecule, or displacing a contact between two atoms, from nearly perfect destructive interference to values of the order of 2e 2/h expected in Kondo systems. We also show that this large conductance change is robust for reasonable temperatures and voltages for symmetric and asymmetric tunnel couplings between the source-drain electrodes and the molecular orbitals. This is relevant for the development of quantum interference effect transistors based on molecular junctions.

A New Race, 704, of Plasmopara helianthi Pathogen of Sunflower Downy Mildew in Italy.

The recent changes of the European Common Agricultural Policy and the market needs of oleaginous crops for energy purposes caused a renewed increase of sunflower (Helianthus annuus L.) cultivation in Italy. During 2006, surveys on approximately 92 ha of Umbrian (central Italy) sunflower fields were carried out for monitoring distribution and race variability of the pathogen. Twelve fields planted with commercial hybrids were surveyed. Downy mildew was only observed in five fields, with 2 to 3% of disease incidence. Systemic mildewed plants showed stunting, leaf chlorosis, and sporulation on the underside of leaf surface. Pathogen inocula were directly recovered from infected leaves by brushing the fungal structures or after infected leaves were incubated in a humid chamber at 18 to 20°C in the dark for 24 to 48 h. After increasing initial inocula on the suscpetible cv. Ala, race identification of four isolates was determined by the reaction of three standard sets of nine differential sunflower lines using a triplet code (3). Thirty to forty pregerminated seeds for each differential line (three replicates per line) were inoculated by the whole-seedling immersion technique (1). After 12 days, plants were maintained at 20°C and 100% relative humidity for 24 to 48 h to enhance pathogen sporulation and evaluate for susceptible (sporulation on cotyledons and/or first true leaves) or resistance (absence of sporulation or weak sporulation only on cotyledons) reactions. Inoculation tests were performed twice. The isolates were also evaluated for their sensitivity to metalaxyl-M (Apron XL 31.8%) used at the Italian registered rate (1.05 g of a.i. per kg of seed). Treated and untreated seeds of cv. Ala (50 seeds per pot with three replicates) were sown into pots filled with a sterilized sandy-loam mixture (1:1, vol/vol). Five days after sowing, soil drench inoculation was performed by spreading over the pots (80 ml per pot) a zoosporangia suspension (1 to 2 × 104 zoosporangia per ml) of each isolate. Disease incidence (DI) was determined by counting the number of uninfected and infected plants (sporulation on cotyledons and/or true leaves). Hypocotyls of plants that seemed uninfected were cut into sections (2 to 3 cm long) and placed in a humid chamber to allow pathogen sporulation. The experiments were performed twice. Three isolates were characterized as race 700 and one as a mixture of races 700 and 704. Race 700 is more widespread in Italy, whereas race 704 was reported in France in 2002 (2). All Plasmopara helianthi isolates produced 84 to 89% infection on plants from untreated seeds, whereas DI from fungicide treated seeds was significantly lower (8 to 17%). To our knowledge, this is the first report of race 704 in Italy. All field isolates were also metalaxyl-M sensitive as already reported in other European countries (4). References: (1) T. J. Gulya et al. Helia 14:11, 1991. (2) E. Mestries. Oleoscope 83:13, 2005. (3) M. L. Molinero et al. Plant Dis. 86:736, 2002. (4) M. L. Molinero et al. Plant Dis. 87:749, 2003.

cis and trans factors affecting Mos1 mariner evolution and transposition in vitro, and its potential for functional genomics.

Mos1 and other mariner / Tc1 transposons move horizon-tally during evolution, and when transplanted into heterologous species can transpose in organisms ranging from prokaryotes to protozoans and vertebrates. To further develop the Drosophila Mos1 mariner system as a genetic tool and to probe mechanisms affecting the regulation of transposition activity, we developed an in vitro system for Mos1 transposition using purified transposase and selectable Mos1 derivatives. Transposition frequencies of nearly 10(-3)/target DNA molecule were obtained, and insertions occurred at TA dinucleotides with little other sequence specificity. Mos1 elements containing only the 28 bp terminal inverted repeats were inactive in vitro, while elements containing a few additional internal bases were fully active, establishing the minimal cis -acting requirements for transposition. With increasing transposase the transposition frequency increased to a plateau value, in contrast to the predictions of the protein over-expression inhibition model and to that found recently with a reconstructed Himar1 transposase. This difference between the 'natural' Mos1 and 'reconstructed' Himar1 transposases suggests an evolutionary path for down-regulation of mariner transposition following its introduction into a naïve population. The establishment of the cis and trans requirements for optimal mariner transposition in vitro provides key data for the creation of vectors for in vitro mutagenesis, and will facilitate the development of in vivo systems for mariner transposition.

Unilateral laryngeal and hypoglossal paralysis (Tapia's syndrome) following rhinoplasty in general anaesthesia: case report and review of the literature.

Extracranial involvement of the recurrent laryngeal nerve and the hypoglossal nerve is known as Tapia's syndrome. Ipsilateral paralysis of the vocal cord and tongue is present. Lesion of these nerves may be a rare complication of airway management. Herein, a case of Tapia's Syndrome complicating transoral intubation during general anaesthesia in a rhinoplasty operation, together with a review of pertinent literature to evaluate the incidence and the possible pathogenic mechanism of the lesion. There are recent reports in the literature on mono or bilateral paralysis of the XII or laryngeal recurrent nerve after use of laryngeal mask with a pathogenic mechanism of compression. Furthermore, there are reports, following oro-tracheal intubation, of recurrent laryngeal paralysis, likely legacies to the compression of the anterior branch of inferior laryngeal nerve by the cuff of the oro-tracheal tube against the postero-medial part of the thyroid cartilage. Hypoglossal nerve damage could be caused by a stretching of the nerve against the greater horn of the hyoid bone by a laryngeal mask or oro-tracheal tube or compression of the posterior part of the laryngoscope or oro-tracheal tube. In our case, the lesion probably occurred as the result of a two-fold compressive mechanism: on one hand, compression by the cuff of the endo-tracheal tube due to excessive throat pack in the oro-pharynx; on the other hand a prolonged stretching mechanism of these nerves may have occurred due to excessive anterior and lateral flexion of the head. From the data reported in the literature, as in our case, complete recovery of function is generally achieved within the first six months. This progressive recovery of function suggests nerve damage of a neuro-praxic type, which is typical of compression injury. In conclusion, the response of this rare complication confirms the importance not only of the position of the head and patient on the operating table but also the meticulous and correct performance of the routine manoeuvres of airway management.

In vitro methylation of histones in sea urchin nuclei during early embryogenesis.

Nuclei isolated from sea urchin embryos incubated in vitro in the presence of S-adenosyl-[methyl-3H]methionine, methylate their own basic proteins. The protein methylase activity varies during the embryonic development with two peaks of activity at mesenchymal blastula and at young gastrula. Histones H3 and H4 are the main substrates of the reaction. The extent of methylation of the two histones depends on the S-adenosylmethionine concentration. At low S-adenosylmethionine concentrations, the in vitro methyl-accepting ability of H3 is 10-times that of H4, while at high concentrations it is 3-times that of H4. This finding is clearly evident in the equilibrium saturation experiments with blastula and gastrula nuclei, which both show two distinct Km values for S-adenosylmethionine. The major and perhaps only product of methylation is epsilon-N-methyl-lysine. Enzyme activity is clearly correlated with specific embryonic stages, while no correlation is apparent between enzyme activity and the amount of DNA in the embryos.

Ceruloplasmin-anion interaction. A circular dichroism spectroscopic study.

The effect of anion binding to ceruloplasmin has been studied using absorption and cirbular dichroism spectral data. At anion to ceruloplasmin molar ratios approaching infinite, OCN-, N3- and SCN- bind to ceruloplasmin giving rise to similar alterations in circular dichroism and absorption spectra. The positive bands at 610 and 520 nm in circular dichroism spectra disappear, a negative one apperars at 600 nm and the peak at 450 nm is only slightly modified. There is a new negative band at 410 nm well-defined in OCN- ceruloplasmin spectra. The decrease in absorption at 610 nm is ascribed to the disruption of one type I Cu-S(cysteine) bond owing presumably to the changes induced by anions in the protein secondary structure. The new band at 410 nm is assigned to a charge transfer transition from the ligand replacing cysteine at its binding site. Both absorption and circular dichroism spectra show isobestic points indicating that anion binding to the enzyme, disruption of one of the two type I Cu-S bonds and coordination of this Cu to another protein residue take place simultaneously.

Histone-lysine methyltransferase activity from sea-urchin embryo nuclei. Changes in substrate specificity upon purification.

The S-adenosylmethionine:histone-lysine methyltransferase (EC 2.1.1.43) enzyme activity, present in the chromatin of sea-urchin embryo nuclei, has been purified about 300-fold with 30% overall yield. The initial activity in the nucleus transfers methyl groups to the epsilon-amino group of lysines and acceptor proteins are chromatin-bound H3 and H4 histones. In contrast, the purified enzyme activity transfers methyl groups to the arginines and acceptor proteins are soluble H3 and H4 histones. The two changes in substrate specificity do not occur at the same time. The variation of acceptor protein from chromatin-bound to soluble histones occurs at the first step, upon nuclei sonication, when no protein fractionation has yet been performed. At that step, lysine is still the only methylated side-chain. The variation of the methylated amino acid from lysine to arginine occurs gradually with increasing enzyme purification. The enzyme activity has a molecular mass of about 200 kDa. Saturation curves for H3 and H4 histones, used as substrate either individually or in total histones, and for AdoMet show no substantial dependence on enzyme purification. Maximal activity for the enzyme, at all purification levels, occurs at about pH 8 for all substrate histones. An increase in the relative concentrations of di- and trimethyllysine derivatives is observed with the more purified enzyme preparations, while the ratio of mono- and dimethylarginine derivatives remains constant. The data are taken as evidence that the same protein molecule is responsible for the two activities.

Restoring the SU(4) Kondo regime in a double quantum dot system.

We calculate the spectral density and occupations of a system of two capacitively coupled quantum dots, each one connected to its own pair of conducting leads, in a regime of parameters in which the total couplings to the leads for each dot Γ(i) are different. The system has been used recently to perform pseudospin spectroscopy by controlling independently the voltages of the four leads. For an odd number of electrons in the system, equal coupling to the leads Γ1 = Γ2, equal dot levels E1 = E2 and sufficiently large interdot repulsion U12 the system lies in the SU(4) symmetric point of spin and pseudospin degeneracy in the Kondo regime. In the more realistic case Γ1 ≠ Γ2, pseudospin degeneracy is broken and the symmetry is reduced to SU(2). Nevertheless, we find that the essential features of the SU(4) symmetric case are recovered by appropriately tuning the level difference δ = E2 - E1. After this tuning, the system behaves as an SU(4) Kondo one at low energies. Our results are relevant for experiments which look for signatures of SU(4) symmetry in the Kondo regime of similar systems.

Coherent manipulation of Andreev states in superconducting atomic contacts.

Coherent control of quantum states has been demonstrated in a variety of superconducting devices. In all of these devices, the variables that are manipulated are collective electromagnetic degrees of freedom: charge, superconducting phase, or flux. Here we demonstrate the coherent manipulation of a quantum system based on Andreev bound states, which are microscopic quasi-particle states inherent to superconducting weak links. Using a circuit quantum electrodynamics setup, we performed single-shot readout of this Andreev qubit. We determined its excited-state lifetime and coherence time to be in the microsecond range. Quantum jumps and parity switchings were observed in continuous measurements. In addition to having possible quantum information applications, such Andreev qubits are a test-bed for the physics of single elementary excitations in superconductors.

New Mos1 mariner transposons suitable for the recovery of gene fusions in vivo and in vitro.

The Drosophila Mos1 element can be mobilized in species ranging from prokaryotes to protozoans and vertebrates, and the purified transposase can be used for in vitro transposition assays. In this report we developed a 'mini-Mos1' element and describe a number of useful derivatives suitable for transposon mutagenesis in vivo or in vitro. Several of these allow the creation and/or selection of tripartite protein fusions to a green fluorescent protein-phleomycin resistance (GFP-PHLEO) reporter/selectable marker. Such X-GFP-PHLEO-X fusions have the advantage of retaining 5' and 3' regulatory information and N- and C-terminal protein targeting domains. A Mos1 derivative suitable for use in transposon-insertion mediated linker insertion (TIMLI) mutagenesis is described, and transposons bearing selectable markers suitable for use in the protozoan parasite Leishmania were made and tested. A novel 'negative selection' approach was developed which permits in vitro assays of transposons lacking bacterial selectable markers. Application of this assay to several Mos1 elements developed for use in insects suggests that the large mariner pM[cn] element used previously in vivo is poorly active in vitro, while the Mos1-Act-EGFP transposon is highly active.

Insertional mutagenesis by a modified in vitro Ty1 transposition system.

Transposable elements are useful tools for insertional mutagenesis and have many potential applications in the characterization of complex genomes. Here we describe a system which facilitates the construction of large transposon insertion libraries useful for genome sequencing and functional genomic analysis. We developed two transposons, TyK and TyK'GFP+, which can be introduced into target DNAs by Ty1-mediated transposition in vitro, and several modifications which decrease the frequency of false transposition events and direct the recovery of transpositions into passenger rather than vector DNA. Insertions of TyK'GFP+ additionally may yield fusions to the Aequorea green fluorescent protein (GFP), useful in studies of gene expression and protein targeting. Transposition in vitro was obtained into target DNAs of up to 50 kb in size, restriction mapping showed insertion to be relatively random, and the sequence of 55 insertion sites showed neither strong site nor base compositional preference. Our data suggest that TyK-based artificial transposons will be suitable for a variety of genetic applications in many organisms.

DNA methyltransferase activity in the early stages of a sea urchin embryo. Evidence of differential control.

The specific activity of DNA methyltransferase increases in the nuclei of Sphaerechinus granularis sea urchin embryos at increasing stages of development. The activity reaches maximal value at about 20 h of growth, when embryos are at the mesenchyme blastula stage, then abruptly decreases and is essentially zero at about 35 h of development, when embryos are at the early gastrula stage. Both the increase and the drop of the activity are faster than embryonic cell duplication indicating that the enzyme is under strict control during development and that, in the more advanced embryo, a mechanism is activated to specifically block its activity.

Characterisation of three chromosomal ends of Leishmania major reveals transcriptional activity across arrays of reiterated and unique sequences.

The 36 chromosomes of the parasite Leishmania major range in size from 200 kb to approximately 2.5 Mb and variation between homologues seems to be restricted to the telomeric and subtelomeric regions. We have isolated three cosmids carrying the telomere hexameric repeat and assigned them to the extreme location of chromosomes 3, 7 and 20. When considering the distribution of repetitive sequences, Southern analysis of the three chromosomal ends indicated the existence of at least two classes of chromosomal extremities: one of them is composed almost exclusively of unique sequences and the other is characterised by patches of both reiterated and unique sequences. We devised a transfection-based strategy that allowed the determination of a map of transcripts in each of the regions examined. Sequencing of the chromosome 20 cosmid revealed the existence of a novel class of reiterated sequence, LST-R378, and 10 ORFs drawing a map of putative genes compatible with the map of transcripts.