Neutrino induced coherent charged pion production on nuclei, ν¯μA→μ±π∓A, is a rare inelastic interaction in which the four-momentum squared transferred to the nucleus is nearly zero, leaving it ...intact. We identify such events in the scintillator of MINERvA by reconstructing |t| from the final state pion and muon momenta and by removing events with evidence of energetic nuclear recoil or production of other final state particles. We measure the total neutrino and antineutrino cross sections as a function of neutrino energy between 2 and 20 GeV and measure flux integrated differential cross sections as a function of Q2, Eπ, and θπ. The Q2 dependence and equality of the neutrino and antineutrino cross sections at finite Q2 provide a confirmation of Adler’s partial conservation of axial current hypothesis.
Processes catalyzed by enzymes offer numerous advantages over chemical methods although in many occasions the stability of the biocatalysts becomes a serious concern. Traditionally, synthesis of ...nucleosides using poorly water-soluble purine bases, such as guanine, xanthine, or hypoxanthine, requires alkaline pH and/or high temperatures in order to solubilize the substrate. In this work, we demonstrate that the 2′-deoxyribosyltransferase from
Leishmania mexicana
(
Lm
PDT) exhibits an unusually high activity and stability under alkaline conditions (pH 8–10) across a broad range of temperatures (30–70 °C) and ionic strengths (0–500 mM NaCl). Conversely, analysis of the crystal structure of
Lm
PDT together with comparisons with hexameric, bacterial homologues revealed the importance of the relationships between the oligomeric state and the active site architecture within this family of enzymes. Moreover, molecular dynamics and docking approaches provided structural insights into the substrate-binding mode. Biochemical characterization of
Lm
PDT identifies the enzyme as a type I NDT (PDT), exhibiting excellent activity, with specific activity values 100- and 4000-fold higher than the ones reported for other PDTs. Interestingly,
Lm
PDT remained stable during 36 h at different pH values at 40 °C. In order to explore the potential of
Lm
PDT as an industrial biocatalyst, enzymatic production of several natural and non-natural therapeutic nucleosides, such as vidarabine (ara A), didanosine (ddI), ddG, or 2′-fluoro-2′-deoxyguanosine, was carried out using poorly water-soluble purines. Noteworthy, this is the first time that the enzymatic synthesis of 2′-fluoro-2′-deoxyguanosine, ara G, and ara H by a 2′-deoxyribosyltransferase is reported.
Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable ...subtype-specific risk estimates are lacking.
We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity.
Protein-truncating variants in 5 genes (
,
,
,
, and
) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (
,
,
, and
) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in
and
, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in
,
,
,
,
, and
, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in
,
, and
were associated with a risk of breast cancer overall with a P value of less than 0.001. For
,
, and
, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants.
The results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.).
The total cross sections are important ingredients for the current and future neutrino oscillation experiments. We present measurements of the total charged-current neutrino and antineutrino cross ...sections on scintillator (CH) in the NuMI low-energy beamline using an in situ prediction of the shape of the flux as a function of neutrino energy from 2–50 GeV. This flux prediction takes advantage of the fact that neutrino and antineutrino interactions with low nuclear recoil energy (ν) have a nearly constant cross section as a function of incident neutrino energy. This measurement is the lowest energy application of the low-ν flux technique, the first time it has been used in the NuMI antineutrino beam configuration, and demonstrates that the technique is applicable to future neutrino beams operating at multi-GeV energies. The cross section measurements presented are the most precise measurements to date below 5 GeV.
Ring chromosome 20 (R20) syndrome is a chromosomal disorder characterized mainly by drug-resistant frontal lobe seizures, recurrent nonconvulsive status epilepticus (NCSE), and typical EEG features. ...The aim of this study was to investigate if this triad is common and specific to all patients with R20.
In this cross-sectional study (from 2000 to 2011), we selected patients who fulfilled at least two out of three criteria: drug-resistant frontal lobe seizures, recurrent NCSE, and characteristic electroencephalography (EEG) features. In all patients, diagnosis was based on karyotype analysis of at least 100 metaphases.
We identified 36 patients who met at least two of the selected criteria: six patients (16.7%) with R20 and 30 (83.3%) without R20 (non-R20). All patients with R20 met all three criteria. Eleven (36.7%) patients without R20, however, also displayed the full triad. In 19 patients without R20 (63.3%), one of the three clinical features was missing: frontal lobe seizures were not resistant to antiepileptic drugs (AED) in four (13.3%), recurrent NCSE was missing in six (20%), and nine (30%) patients did not have typical EEG features. Based on this data, specificity was 63.3%, positive predictive value was 35.3%, and sensitivity and negative predictive values were 100%.
Additionally, a review of all publications describing the R20 phenotype revealed that 81.98% of patients with R20 display the full electroclinical triad.
In our study, all patients with R20 displayed the three electroclinical characteristics. This is in line with previous reports (presenting high sensitivity and negative predictive value). However, these features can also be observed in other epilepsies and are not specific to R20. Our findings suggest that in the presence of the full triad of symptoms, karyotype analysis focused on chromosome 20 should be conducted.
•The R20 syndrome is underdiagnosed as a high index of suspicion is required.•The R20 characteristic triad: Refractory frontal seizures, recurrent NCSE, and typical EEG•While not specific, our triad presents high sensitivity and negative predictive value.•In cases of the full triad, karyotype analysis, focused on Chr 20, should be conducted.
Knowledge of the neutrino flux produced by the Neutrinos at the Main Injector (NuMI) beamline is essential to the neutrino oscillation and neutrino interaction measurements of the MINERvA, MINOS+, ...NOvA and MicroBooNE experiments at Fermi National Accelerator Laboratory. We have produced a flux prediction which uses all available and relevant hadron production data, incorporating measurements of particle production off of thin targets as well as measurements of particle yields from a spare NuMI target exposed to a 120 GeV proton beam. The result is the most precise flux prediction achieved for a neutrino beam in the one to tens of GeV energy region. We have also compared the prediction to in situ measurements of the neutrino flux and find good agreement.
Ferns are thought to have lower photosynthetic rates than angiosperms and they lack fine stomatal regulation. However, no study has directly compared photosynthesis in plants of both groups grown ...under optimal conditions in a common environment. We present a common garden comparison of seven angiosperms and seven ferns paired by habitat preference, with the aims of (1) confirming that ferns do have lower photosynthesis capacity than angiosperms and quantifying these differences; (2) determining the importance of diffusional versus biochemical limitations; and (3) analysing the potential implication of leaf anatomical traits in setting the photosynthesis capacity in both groups. On average, the photosynthetic rate of ferns was about half that of angiosperms, and they exhibited lower stomatal and mesophyll conductance to CO₂(gₘ), maximum velocity of carboxylation and electron transport rate. A quantitative limitation analysis revealed that stomatal and mesophyll conductances were co‐responsible for the lower photosynthesis of ferns as compared with angiosperms. However, gₘalone was the most constraining factor for photosynthesis in ferns. Consistently, leaf anatomy showed important differences between angiosperms and ferns, especially in cell wall thickness and the surface of chloroplasts exposed to intercellular air spaces.
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