First Search for Dark-Trident Processes Using the MicroBooNE Detector.

We present a first search for dark-trident scattering in a neutrino beam using a dataset corresponding to 7.2×10^{20} protons on target taken with the MicroBooNE detector at Fermilab. Proton interactions in the neutrino target at the main injector produce π^{0} and η mesons, which could decay into dark-matter (DM) particles mediated via a dark photon A^{'}. A convolutional neural network is trained to identify interactions of the DM particles in the liquid-argon time projection chamber (LArTPC) exploiting its imagelike reconstruction capability. In the absence of a DM signal, we provide limits at the 90% confidence level on the squared kinematic mixing parameter ϵ^{2} as a function of the dark-photon mass in the range 10≤M_{A^{'}}≤400 MeV. The limits cover previously unconstrained parameter space for the production of fermion or scalar DM particles χ for two benchmark models with mass ratios M_{χ}/M_{A^{'}}=0.6 and 2 and for dark fine-structure constants 0.1≤α_{D}≤1.

First Measurement of η Meson Production in Neutrino Interactions on Argon with MicroBooNE.

We present a measurement of η production from neutrino interactions on argon with the MicroBooNE detector. The modeling of resonant neutrino interactions on argon is a critical aspect of the neutrino oscillation physics program being carried out by the DUNE and Short Baseline Neutrino programs. η production in neutrino interactions provides a powerful new probe of resonant interactions, complementary to pion channels, and is particularly suited to the study of higher-order resonances beyond the Δ(1232). We measure a flux-integrated cross section for neutrino-induced η production on argon of 3.22±0.84(stat)±0.86(syst) 10^{-41} cm^{2}/nucleon. By demonstrating the successful reconstruction of the two photons resulting from η production, this analysis enables a novel calibration technique for electromagnetic showers in GeV accelerator neutrino experiments.

Search for Heavy Neutral Leptons in Electron-Positron and Neutral-Pion Final States with the MicroBooNE Detector.

We present the first search for heavy neutral leptons (HNLs) decaying into νe^{+}e^{-} or νπ^{0} final states in a liquid-argon time projection chamber using data collected with the MicroBooNE detector. The data were recorded synchronously with the NuMI neutrino beam from Fermilab's main injector corresponding to a total exposure of 7.01×10^{20} protons on target. We set upper limits at the 90% confidence level on the mixing parameter |U_{µ4}|^{2} in the mass ranges 10≤m_{HNL}≤150 MeV for the νe^{+}e^{-} channel and 150≤m_{HNL}≤245 MeV for the νπ^{0} channel, assuming |U_{e4}|^{2}=|U_{τ4}|^{2}=0. These limits represent the most stringent constraints in the mass range 35

First Double-Differential Measurement of Kinematic Imbalance in Neutrino Interactions with the MicroBooNE Detector.

We report the first measurement of flux-integrated double-differential quasielasticlike neutrino-argon cross sections, which have been made using the Booster Neutrino Beam and the MicroBooNE detector at Fermi National Accelerator Laboratory. The data are presented as a function of kinematic imbalance variables which are sensitive to nuclear ground-state distributions and hadronic reinteraction processes. We find that the measured cross sections in different phase-space regions are sensitive to different nuclear effects. Therefore, they enable the impact of specific nuclear effects on the neutrino-nucleus interaction to be isolated more completely than was possible using previous single-differential cross section measurements. Our results provide precision data to help test and improve neutrino-nucleus interaction models. They further support ongoing neutrino-oscillation studies by establishing phase-space regions where precise reaction modeling has already been achieved.

First Measurement of Quasielastic Λ Baryon Production in Muon Antineutrino Interactions in the MicroBooNE Detector.

We present the first measurement of the cross section of Cabibbo-suppressed Λ baryon production, using data collected with the MicroBooNE detector when exposed to the neutrinos from the main injector beam at the Fermi National Accelerator Laboratory. The data analyzed correspond to 2.2×10^{20} protons on target running in neutrino mode, and 4.9×10^{20} protons on target running in anti-neutrino mode. An automated selection is combined with hand scanning, with the former identifying five candidate Λ production events when the signal was unblinded, consistent with the GENIE prediction of 5.3±1.1 events. Several scanners were employed, selecting between three and five events, compared with a prediction from a blinded Monte Carlo simulation study of 3.7±1.0 events. Restricting the phase space to only include Λ baryons that decay above MicroBooNE's detection thresholds, we obtain a flux averaged cross section of 2.0_{-1.7}^{+2.2}×10^{-40} cm^{2}/Ar, where statistical and systematic uncertainties are combined.

First Constraints on Light Sterile Neutrino Oscillations from Combined Appearance and Disappearance Searches with the MicroBooNE Detector.

We present a search for eV-scale sterile neutrino oscillations in the MicroBooNE liquid argon detector, simultaneously considering all possible appearance and disappearance effects within the 3+1 active-to-sterile neutrino oscillation framework. We analyze the neutrino candidate events for the recent measurements of charged-current ν_{e} and ν_{µ} interactions in the MicroBooNE detector, using data corresponding to an exposure of 6.37×10^{20} protons on target from the Fermilab booster neutrino beam. We observe no evidence of light sterile neutrino oscillations and derive exclusion contours at the 95% confidence level in the plane of the mass-squared splitting Δm_{41}^{2} and the sterile neutrino mixing angles θ_{µe} and θ_{ee}, excluding part of the parameter space allowed by experimental anomalies. Cancellation of ν_{e} appearance and ν_{e} disappearance effects due to the full 3+1 treatment of the analysis leads to a degeneracy when determining the oscillation parameters, which is discussed in this Letter and will be addressed by future analyses.

Towards a closed eye model of the pre-ocular tear layer.

Although the tear film has been extensively studied as it exists in the open eye state, until recently very little was known as to what happens to the tear film on eye closure. Recent studies have shown that eye closure results in a profound change in the composition, origins, turnover and physiological functions of the tear film. These changes include a shift from an inducible, neurologically controlled, lacrimal secretion containing among other proteins primarily lysozyme, lactoferrin and tear specific lipocalin, to a much slower, constitutive-type of secretion, composed almost exclusively of sIgA. This change is accompanied by the build-up of sialoglycoproteins of epithelial and goblet cell origin, the build-up and activation of complement and the build-up of serum proteins. In addition, various cytokines and proinflammatory mediators accumulate, including some which are potent inducers of angiogenesis and leukochemotaxis. The closed eye also exhibits the recruitment and activation of massive numbers of PMN cells. This results in a stagnant, closed eye layer, which is extremely rich in reactive complement products, PMN cell proteases including protease-3, elastase, capthepsin G, MMP-9 and urokinase. We have postulated that this shift represents a fundamental change in host-defense strategies from a passive-barrier defense to an active immune, inflammatory, phagocyte-mediated process and that this shift is necessitated in order to protect the cornea from entrapped microorganisms. Studies have shown that autologous cell damage is avoided in closed eye tear fluid, by the accumulation of several modulators of complement activation, which shift activation towards opsonization of entrapped microorganisms and the build-up of a wide array of antiproteases. Some of the latter are likely to arise from the ocular surface tissues. Corneal neovascularization may be avoided in part by the build-up of alpha2-macroglobulin and the conversion of plasminogen to angiostatin. It is highly probable that other bioactive protein fragments are produced in the closed eye, which contribute to homeostasis. Areas of future study are indicated.

Diurnal variations in tear glycoproteins: evidence for an epithelial origin for the major non-reducible > or = 450 kDa sialoglycoprotein(s).

PURPOSE: To characterize the nature and origin of changes in tear glycoproteins accompanying eye closure. METHODS: Reflex (R) and overnight closed (C) eye tears collected by capillary tubes were centrifuged with the resulting R pellets (primarily desquamated epithelial cells) and C pellets (primarily PMN and some epithelial cells) extracted in acidic PBS. Extracts and supernatants were separated by size-exclusion HPLC and/or SDS-PAGE. Gels were stained or blotted and immune- or lectin-probed. An HPLC glycoprotein fraction of > or = 450 kDa isolated from all four sources was characterized before and after partial deglycosylation, using antibodies specific to known mucin and carbohydrate epitopes. Immunofluorescence microscopy was carried out on human conjunctiva, using as probe a MAb to salivary mucin specific for a sialyl Lea epitope, which was found to cross-react specifically with the major non-reducible high molecular weight sialoglycoproteins (SGs) in tears. These SGs were immunoprecipitated and blot-probed along with tissue extracts. RESULTS: R fluid contained minor amounts of numerous glycoproteins, including probably several of inducible lacrimal secretory origin. Results confirmed sIgA as the principal source of the intense reducible glycoprotein bands common to C fluid. Smaller amounts of free secretory component and serum glycoproteins were also visualized. The HPLC fraction (> or = 450 kDa) consisted of four major non-reducible glycoproteins. In R fluid, this fraction (< 1% total protein) consisted primarily of two entities: a 450-500 kDa SG and a larger asialoglycoprotein. The SG accounts for as much as 85% of the total protein in the R pellet extract. C fluid was associated with a selective increase in SGs and a shift in distribution to two SGs > 500 kDa. All SGs exhibited a common antigenicity reacting specifically with the MAb for the sialyl Lea epitope. SGs indistinguishable in size and antigenicity were recovered in epithelial extracts. Immunofluorescence microscopy revealed that reactivity was localized to the epithelial plasma membrane, increasing in intensity from basal to apical cells. Although these SGs exhibited some properties in common with MUC1, immunological and other data suggest a unique SG. CONCLUSIONS: Tear glycoproteins are derived from four principal sources. In R fluid, an inducible lacrimal secretion predominates. In C fluid, a constitutive sIgA secretion predominates, augmented by a serum exudate and SGs derived at least in part from the epithelium. In R fluid and pellet extracts, the SGs consist primarily of a 450-500 kDa species that is most probably derived from the plasma membrane. Larger antigenically related SGs are prevalent in C fluid.

Evidence for a central role of transcription in the timing mechanism of a circadian clock.

The retinal circadian clock in the isolated in vitro eye of the marine mollusc Bulla gouldiana exhibits a phase-dependent requirement for transcription. The transcription-sensitive phase extends through most of the subjective day and therefore is substantially longer than the previously reported translation-sensitive phase. Lower concentrations of transcription inhibitors yield a significant dose-dependent lengthening of circadian period. Clock motion can be stopped by a high concentration of the transcription inhibitor 5,6-dichlorobenz-imidazole riboside (DRB) when applied during the sensitive phase; after withdrawal of the inhibitor, motion resumes from the phase at which it was stopped. In a double-pulse experiment, phase shifts to light pulses applied after DRB pulses, and not during the translation-sensitive phase, indicate that the inhibition of transcription has immediate effects on the phase of the clock. These data suggest that DRB-induced phase shifts are independent of translation, which implies that the rate of transcription itself plays a significant role in the mechanism underlying the generation of the circadian cycle.

Subarachnoid injection--a potential complication of retrobulbar block.

This study was undertaken to illustrate the potential for subarachnoid injection during retrobulbar block as a cause of respiratory arrest. Cadaver orbits were used to document the connection between the optic nerve sheath and the subarachnoid space. Following dissections of the orbits on one side of 24 cadavers, the optic nerve sheaths were identified and injected with 0.5 ml of water for measurement of pressure generated during injection. This was followed by intrasheath injection of equal volume of methylene blue for demonstrating the subarachnoid space surrounding the optic nerves. All injections were performed with a 1-ml syringe with a one-and-one-half-inch 22-G needle over a period of 10 s. The blue dye was found to track along the subarachnoid space of the optic nerve sheath to the chiasmatic cistern in the middle cranial fossa. Retrobulbar injections were performed on the contralateral undissected orbits and intrascleral injections were performed on undissected eyes. The size of the syringes, the gauge of the needles, and the speed of injection were uniform for all injections. The pressure generated by injection into the optic nerve sheath or intrascleral injection (approximately 138 mmHg) was three- to fourfold that produced by injection into the retrobulbar adipose tissue (approximately 35 mmHg) (P less than 0.05). The authors conclude that any resistance encountered during retrobulbar block should serve as a warning signal, mandating redirection of the needle, in order to prevent subarachnoid injection.

High-performance liquid chromatographic fractionation and partial characterization of cystic fibrosis serum ultrafiltrates.

Analytical separation of serum ultrafiltrates by high-performance liquid chromatography produces a distinctive peak with a retention time of 18.5-21 min (subfraction 18.5) from cystic fibrosis serum ultrafiltrates and obligate heterozygote serum ultrafiltrates, but not in significant concentrations from control or asthmatic serum ultrafiltrates. Semipreparative separation of control serum ultrafiltrates produced a small peak with similar retention time that was approximately 1% of the arbitrary absorbance units found in this cystic fibrosis subfraction. Subfraction 18.5 had biological activity only when separated from cystic fibrosis serum ultrafiltrate, but did not contain measurable amounts of C3a des-arginine and C4a des-arginine. Subfraction 18.5 is a low-molecular-weight material (1000-1400 daltons) that contains 14.9 micrograms orcinol positive material per 50 micrograms protein. The spectrum of subfraction 18.5 indicates that it has to be purified to homogeneity.

Biological activities of cystic fibrosis serum. IV. Stimulation of the calcium mediated K+ efflux from rat submandibular gland fragments.

Cystic fibrosis (CF) and heterozygote sera stimulate a significant K+ efflux from rat submandibular gland fragments in the presence of 1 mM ouabain. This sensitive parameter can be maximally stimulated by as little as 0.5% CF serum and is inhibited by the calcium channel blocker D600 and EGTA. Specific receptor blockers propranolol, phenoxybenzamine or atropine do not inhibit the CF serum-stimulated K+ efflux and agonists do not supramaximally stimulate K+ efflux when added with serum. CF serum-induced K+ efflux did not result in the leakage of lactic dehydrogenase into the bathing media nor did it mimic the action of the calcium ionophore A23187 when added in the presence of D600. In addition, ultrafiltrates of CF serum (less than 10,000 daltons) also stimulated K+ efflux from rat submandibular gland tissue fragments.

Agonist-induced secretions and potassium release from rat submandibular gland slices.

Secretory activity induced by stimulation of alpha-adrenergic, beta-adrenergic, and muscarinic cholingeric receptors and by dibutyryl cAMP and 8-bromo cGMP has been investigated in rat submandibular tissue slices. Isoproterenol produced a sialic acid secretion from the acinar cells that was inhibited by propranolol, but not by phenoxybenzamine or atropine. Dibutyryl cAMP produced a sialic acid secretion from the acinar cells that was not inhibited by propranolol, phenoxybenzamine, or atropine. Both norepinephrine and acetylcholine produced significant secretion of sialic acid but at a reduced efficacy. Norepinephrine stimulated both peptide hydrolase secretion from the granular duct cells and a release of K+ from the acinar cells. Both actions were inhibited by phenoxybenzamine, but not by propranolol or atropine. Acetylcholine stimulated a minimal secretion of peptide hydrolase from the granular duct cells and a significant release of K+ from the acinar cells. The norepinephrine- and acetylcholine-stimulated release of K+ was increased after the addition of 1 mM ouabain. High concentrations of 8-bromo cGMP induced a K+ efflux that was not inhibited by phenoxybenzamine or atropine. Vacuolation of the acinar cells was correlated with K+ release.

The biologic activities of cystic fibrosis serum. II. Ultrastructural aspects of the effect of cystic fibrosis sera and calcium ionophore A23187 on rabbit tracheal explants.

Ultrastructural and cytochemical observations indicate that both cystic fibrosis (CF) sera and calcium ionophore A23187 induce a swelling or an increase in the size and possibly the number of secondary lysosomes and an increase in mucus secretion in epithelium of the rabbit tracheal bioassay system. Extended incubation of the rabbit tracheal explants with either CF or control sera produces a cytotoxic effect on the tracheal epithelium, but only after the termination of the normal bioassay time period. Comparative ultrastructural study of the effect of both CF sera and calcium ionophore A23187 on the rabbit tracheal bioassay system indicates that increased membrane permeability to calcium may be important in the production of the ciliary dyskinesia response by CF serum factor(s) in the rabbit tracheal bioassay system.

Electron microscopic autoradiographic analysis of the uptake and intracellular transport of H3-leucine by the rat submandibular gland acinar cells in tissue slices.

Uptake of H3-leucine into secretory product and its subsequent intracellular transport was analyzed by electron microscopic autoradiographic techniques in the rat submandibular gland acinar cells in vitro. The route and kinetic timetable of intracellular transport was established for the acinar cell secretory product by calculating the present of silver grains and relative grain density associated with the various organelles on a time sequence basis. Radioactivity was first associated with the rough endoplasmic reticulum; then the convex surface of the Golgi apparatus; the concave surface of the Golgi apparatus; and finetics of intracellular transport in the rat submandibular gland acinar cell with other established systems revealed only a difference in the exit of radioactivity from the concave surface of the Golgi apparatus.

The biologic activities of cystic fibrosis serum. I. The effects of cystic fibrosis sera and calcium ionophore A 23187 on rabbit tracheal explants.

An ionophore A23187-induced increase in membrane permeability to calcium ions in culture medium produced a rabbit tracheal mucociliary response indistinguishable from that caused by cystic fibrosis (CF) sera on three different occasions. Specific chelation of calcium ions with EGTA in the basal medium Eagle (BME) media with no additive or in native CF sera abolished the mucociliary disturbances in all cases. Increased membrane permeability to calcium may be important in the production of the mucociliary response by CF serum factor(s) in the tracheal assay system.