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1.
Phys Rev Lett ; 132(16): 162501, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38701469

ABSTRACT

The electromagnetic form factors of the proton and neutron encode information on the spatial structure of their charge and magnetization distributions. While measurements of the proton are relatively straightforward, the lack of a free neutron target makes measurements of the neutron's electromagnetic structure more challenging and more sensitive to experimental or model-dependent uncertainties. Various experiments have attempted to extract the neutron form factors from scattering from the neutron in deuterium, with different techniques providing different, and sometimes large, systematic uncertainties. We present results from a novel measurement of the neutron magnetic form factor using quasielastic scattering from the mirror nuclei ^{3}H and ^{3}He, where the nuclear effects are larger than for deuterium but expected to largely cancel in the cross-section ratios. We extracted values of the neutron magnetic form factor for low-to-modest momentum transfer, 0.6

2.
Phys Rev Lett ; 132(15): 151801, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38683006

ABSTRACT

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.

3.
Phys Rev Lett ; 132(4): 041801, 2024 Jan 26.
Article in English | MEDLINE | ID: mdl-38335355

ABSTRACT

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

4.
Phys Rev Lett ; 131(10): 101802, 2023 Sep 08.
Article in English | MEDLINE | ID: mdl-37739352

ABSTRACT

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.

5.
Phys Rev Lett ; 130(23): 231802, 2023 Jun 09.
Article in English | MEDLINE | ID: mdl-37354393

ABSTRACT

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.


Subject(s)
Mesons , Protons , Computer Simulation , Monte Carlo Method
6.
JDR Clin Trans Res ; : 23800844231165016, 2023 Apr 21.
Article in English | MEDLINE | ID: mdl-37082861

ABSTRACT

PURPOSE: We aim to understand the impact of the COVID-19 on health care utilization and oral health conditions of patients at federally qualified health centers (FQHCs), where patients are disproportionately low income, publicly insured, or uninsured. METHODS: Using deidentified electronic health records of patients at FQHCs in the United States from January 2019 through December 2020 (n = 431,509), variations in health care utilization since the COVID-19 outbreak were observed by procedure types and patient characteristics. Changes in dental utilization and oral health conditions were characterized using mixed-effect negative binomial and logistic regression models. RESULTS: Dental utilization decreased more drastically than medical utilization during shelter-in-place periods in 2020 and rebounded more slowly after the reopening. Greater demands for oral surgery and teledentistry and less demands for preventive services were observed in 2020. As compared to 2019, patients experienced more psychological stress-related dental conditions with odds ratios of 1.52 (95% confidence interval [CI], 1.31-1.76) for uninsured, 1.48 (95% CI, 1.07-2.02) for Medicaid enrollees, and 2.38 (95% CI, 1.68-3.40) for private insurance beneficiaries. CONCLUSION: As a result of COVID-19, patients received more invasive dental procedures due to delayed treatment and experienced a higher risk of psychological stress-related dental conditions. Continued support for statewide policies to expand access to oral health care and oral health promotion strategies for the vulnerable populations would be encouraged. KNOWLEDGE TRANSFER STATEMENT: Our study describes the impact of COVID-19 on dental care use and oral health conditions at Federally Qualified Health Centers, targeted to provide care for some of the most vulnerable populations in the United States. The results of this retrospective cohort study can be used by clinicians and policymakers on understanding the clinical needs of the vulnerable populations after the pandemic. It highlights the need for continued support to expand access to oral health care and oral health promotion to these populations.

7.
Phys Rev Lett ; 130(1): 011801, 2023 Jan 06.
Article in English | MEDLINE | ID: mdl-36669216

ABSTRACT

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.

8.
Nature ; 609(7925): 41-45, 2022 09.
Article in English | MEDLINE | ID: mdl-36045235

ABSTRACT

When protons and neutrons (nucleons) are bound into atomic nuclei, they are close enough to feel significant attraction, or repulsion, from the strong, short-distance part of the nucleon-nucleon interaction. These strong interactions lead to hard collisions between nucleons, generating pairs of highly energetic nucleons referred to as short-range correlations (SRCs). SRCs are an important but relatively poorly understood part of nuclear structure1-3, and mapping out the strength and the isospin structure (neutron-proton (np) versus proton-proton (pp) pairs) of these virtual excitations is thus critical input for modelling a range of nuclear, particle and astrophysics measurements3-5. Two-nucleon knockout or 'triple coincidence' reactions have been used to measure the relative contribution of np-SRCs and pp-SRCs by knocking out a proton from the SRC and detecting its partner nucleon (proton or neutron). These measurements6-8 have shown that SRCs are almost exclusively np pairs, but they had limited statistics and required large model-dependent final-state interaction corrections. Here we report on measurements using inclusive scattering from the mirror nuclei hydrogen-3 and helium-3 to extract the np/pp ratio of SRCs in systems with a mass number of three. We obtain a measure of the np/pp SRC ratio that is an order of magnitude more precise than previous experiments, and find a marked deviation from the near-total np dominance observed in heavy nuclei. This result implies an unexpected structure in the high-momentum wavefunction for hydrogen-3 and helium-3. Understanding these results will improve our understanding of the short-range part of the nucleon-nucleon interaction.

9.
Phys Rev Lett ; 128(21): 212503, 2022 May 27.
Article in English | MEDLINE | ID: mdl-35687456

ABSTRACT

An unexplained >4σ discrepancy persists between "beam" and "bottle" measurements of the neutron lifetime. A new model proposed that conversions of neutrons n into mirror neutrons n^{'}, part of a dark mirror sector, can increase the apparent neutron lifetime by 1% via a small mass splitting Δm between n and n^{'} inside the 4.6 T magnetic field of the National Institute of Standards and Technology Beam Lifetime experiment. A search for neutron conversions in a 6.6 T magnetic field was performed at the Spallation Neutron Source which excludes this explanation for the neutron lifetime discrepancy.

10.
Eur Phys J C Part Fields ; 81(4): 322, 2021.
Article in English | MEDLINE | ID: mdl-34720713

ABSTRACT

The Deep Underground Neutrino Experiment (DUNE) will be a powerful tool for a variety of physics topics. The high-intensity proton beams provide a large neutrino flux, sampled by a near detector system consisting of a combination of capable precision detectors, and by the massive far detector system located deep underground. This configuration sets up DUNE as a machine for discovery, as it enables opportunities not only to perform precision neutrino measurements that may uncover deviations from the present three-flavor mixing paradigm, but also to discover new particles and unveil new interactions and symmetries beyond those predicted in the Standard Model (SM). Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNE's sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, neutrino trident production, dark matter from both beam induced and cosmogenic sources, baryon number violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach.

11.
J Dent Res ; 100(1): 50-57, 2021 01.
Article in English | MEDLINE | ID: mdl-32857641

ABSTRACT

Unemployment rates in the United States are rapidly increasing as a result of the COVID-19 pandemic and attendant economic disruption. As employees lose their jobs, many will lose their employer-sponsored dental insurance (ESDI). Changes in insurance coverage are directly related to the oral health of the population, with many at risk of losing access to dental care. We assessed the impact of recent unemployment rates on insurance coverage and dental utilization. We estimated changes in dental insurance coverage at the state level, using previously applied econometric estimates. Expected changes in types of dental procedures performed at dental practices nationwide were assessed using a microsimulation model, using national practice survey data. Changes in emergency department (ED) visits for dental problems were estimated by fitting trendlines to ED visit patterns by payer type. Sensitivity analyses were conducted to assess how variations in unemployment rates and rates of ESDI in response to unemployment could alter the results. Since March 2020, the national unemployment rate has increased by 8.40 percentage points, an increase expected to result in more than 16 million individuals losing ESDI in the United States. Of these individuals, 45.0% are likely to enroll in their state's Medicaid and Children's Health Insurance Program, and 47.0% are expected to become uninsured. With these expected changes in dental insurance coverage, the average dental practice would experience decreases in routine checkup visits but increases in tooth extraction, a procedure that is highly used by publicly insured or uninsured patients. In addition, dental-related ED visits would be expected to grow by 4.0%. Losses of employment caused by the COVID-19 in the United States can have countervailing effects on people's health by impeding access to dental care. Lack of dental insurance is expected to be more pronounced in states that have not expanded Medicaid or do not provide Medicaid dental benefits for adults.


Subject(s)
COVID-19/economics , Insurance Coverage , Insurance, Dental , Pandemics/economics , Adult , Children's Health Insurance Program , Dentistry , Humans , Medicaid , Medically Uninsured/statistics & numerical data , Unemployment/statistics & numerical data , United States
12.
Ir Med J ; 110(10): 660, 2017 12 18.
Article in English | MEDLINE | ID: mdl-29465850

ABSTRACT

Diabetes mellitus is a common disorder of glucose metabolism that is increasingly prevalent in the Irish population. It is associated with a range of complications leading to substantial morbidity and mortality. A less well-recognized complication of diabetes is periodontal disease. This is a chronic inflammatory disease affecting the periodontium, the specialized group of tissues that surround and support the teeth, including the gingiva (gums) and alveolar bone. Periodontal disease affects patients with diabetes with a greater prevalence and incidence than non-diabetic patients, and can itself exert negative effects on glucose control in people with diabetes. The National Clinical Programme for Diabetes in Ireland aims to reduce the morbidity and mortality associated with diabetes, which includes the development and dissemination of guidelines supporting integrated care. Based on the bidirectional relationship between diabetes mellitus and periodontal disease, we recommend that an oral health evaluation, as well as any necessary onward referral, be incorporated into the Irish recommendations for routine diabetes care, as part of the National Clinical Programme.


Subject(s)
Diabetes Complications/therapy , Diabetes Mellitus/therapy , Oral Health , Periodontal Diseases/etiology , Humans , Ireland , Periodontal Diseases/therapy
13.
Phys Rev Lett ; 113(12): 123002, 2014 Sep 19.
Article in English | MEDLINE | ID: mdl-25279624

ABSTRACT

Spectra of molecular hydrogen (H2) are employed to search for a possible proton-to-electron mass ratio (µ) dependence on gravity. The Lyman transitions of H2, observed with the Hubble Space Telescope towards white dwarf stars that underwent a gravitational collapse, are compared to accurate laboratory spectra taking into account the high temperature conditions (T∼13 000 K) of their photospheres. We derive sensitivity coefficients Ki which define how the individual H2 transitions shift due to µ dependence. The spectrum of white dwarf star GD133 yields a Δµ/µ constraint of (-2.7±4.7stat±0.2syst)×10(-5) for a local environment of a gravitational potential ϕ∼10(4) ϕEarth, while that of G29-38 yields Δµ/µ=(-5.8±3.8stat±0.3syst)×10(-5) for a potential of 2×10(4) ϕEarth.

14.
J Appl Physiol (1985) ; 104(2): 429-38, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18063805

ABSTRACT

AMP-activated protein kinase (AMPK) has been identified as a regulator of gene transcription, increasing mitochondrial proteins of oxidative metabolism as well as hexokinase expression in skeletal muscle. In mice, muscle-specific knockout of LKB1, a component of the upstream kinase of AMPK, prevents contraction- and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR)-induced activation of AMPK in skeletal muscle, and the increase in hexokinase II protein that is normally observed with chronic AICAR activation of AMPK. Since previous reports show a cAMP response element in the promoter region of the hexokinase II gene, we hypothesized that the cAMP-response element (CRE) binding protein (CREB) family of transcription factors could be targets of AMPK. Using radioisotopic kinase assays, we found that recombinant and rat liver and muscle AMPK phosphorylated CREB1 at the same site as cAMP-dependent protein kinase (PKA). AMPK was also found to phosphorylate activating transcription factor 1 (ATF1), CRE modulator (CREM), and CREB-like 2 (CREBL2), but not ATF2. Treatment of HEK-293 cells stably transfected with a CREB-driven luciferase reporter with AICAR increased luciferase activity approximately threefold over a 24-h time course. This increase was blocked with compound C, an AMPK inhibitor. In addition, AICAR-induced activation of AMPK in incubated rat epitrochlearis muscles resulted in an increase in both phospho-acetyl-CoA carboxylase and phospho-CREB. We conclude that CREB and related proteins are direct downstream targets for AMPK and are therefore likely involved in mediating some effects of AMPK on expression of genes having a CRE in their promoters.


Subject(s)
Cyclic AMP Response Element-Binding Protein/metabolism , Liver/metabolism , Multienzyme Complexes/metabolism , Muscle, Skeletal/metabolism , Protein Serine-Threonine Kinases/metabolism , Signal Transduction , AMP-Activated Protein Kinases , Acetyl-CoA Carboxylase/metabolism , Activating Transcription Factor 1/metabolism , Aminoimidazole Carboxamide/analogs & derivatives , Aminoimidazole Carboxamide/pharmacology , Animals , Cell Line , Cyclic AMP Response Element Modulator/metabolism , Cyclic AMP Response Element-Binding Protein/genetics , Cyclic AMP-Dependent Protein Kinases/metabolism , Enzyme Activation , Enzyme Induction , Genes, Reporter , Hexokinase/biosynthesis , Humans , Liver/drug effects , Liver/enzymology , Luciferases , Male , Mice , Mice, Knockout , Multienzyme Complexes/antagonists & inhibitors , Muscle, Skeletal/drug effects , Muscle, Skeletal/enzymology , Phosphorylation , Promoter Regions, Genetic , Protein Kinase Inhibitors/pharmacology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Protein Serine-Threonine Kinases/deficiency , Protein Serine-Threonine Kinases/genetics , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Rats , Rats, Wistar , Recombinant Proteins/metabolism , Ribonucleotides/pharmacology , Signal Transduction/drug effects , Time Factors , Transfection
15.
Am J Physiol Endocrinol Metab ; 293(6): E1572-9, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17925454

ABSTRACT

5'-AMP-activated protein kinase (AMPK), by way of its inhibition of acetyl-CoA carboxylase (ACC), plays an important role in regulating malonyl-CoA levels and the rate of fatty acid oxidation in skeletal and cardiac muscle. In these tissues, LKB1 is the major AMPK kinase and is therefore critical for AMPK activation. The purpose of this study was to determine how the lack of muscle LKB1 would affect malonyl-CoA levels and/or fatty-acid oxidation. Comparing wild-type (WT) and skeletal/cardiac muscle-specific LKB1 knockout (KO) mice, we found that the 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR)-stimulated decrease in malonyl-CoA levels in WT heart and quadriceps muscles was entirely dependent on the presence of LKB1, as was the AICAR-induced increase in fatty-acid oxidation in EDL muscles in vitro, since these responses were not observed in KO mice. Likewise, the decrease in malonyl-CoA levels after muscle contraction was attenuated in KO gastrocnemius muscles, suggesting that LKB1 plays an important role in promoting the inhibition of ACC, likely by activation of AMPK. However, since ACC phosphorylation still increased and malonyl-CoA levels decreased in KO muscles (albeit not to the levels observed in WT mice), whereas AMPK phosphorylation was entirely unresponsive, LKB1/AMPK signaling cannot be considered the sole mechanism for inhibiting ACC during and after muscle activity. Regardless, our results suggest that LKB1 is an important regulator of malonyl-CoA levels and fatty acid oxidation in skeletal muscle.


Subject(s)
Fatty Acids/metabolism , Malonyl Coenzyme A/metabolism , Muscle, Skeletal/metabolism , Protein Serine-Threonine Kinases/metabolism , AMP-Activated Protein Kinase Kinases , AMP-Activated Protein Kinases , Acetyl-CoA Carboxylase/metabolism , Adenosine Monophosphate/metabolism , Aminoimidazole Carboxamide/analogs & derivatives , Aminoimidazole Carboxamide/pharmacology , Animals , Body Weight/genetics , Electric Stimulation , Female , Heart/drug effects , Hypoglycemic Agents/pharmacology , Male , Mice , Mice, Inbred Strains , Mice, Knockout , Multienzyme Complexes/genetics , Multienzyme Complexes/metabolism , Muscle Contraction/drug effects , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/drug effects , Myocardium/metabolism , Oxidation-Reduction/drug effects , Phosphorylation/drug effects , Protein Kinases/chemistry , Protein Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Recombinant Proteins/metabolism , Ribonucleotides/pharmacology
16.
Am J Physiol Endocrinol Metab ; 292(1): E196-202, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16926377

ABSTRACT

LKB1 has been identified as a component of the major upstream kinase of AMP-activated protein kinase (AMPK) in skeletal muscle. To investigate the roles of LKB1 in skeletal muscle, we used muscle-specific LKB1 knockout (MLKB1KO) mice that exhibit low expression of LKB1 in heart and skeletal muscle, but not in other tissues. The importance of LKB1 in muscle physiology was demonstrated by the observation that electrical stimulation of the muscle in situ increased AMPK phosphorylation and activity in the wild-type (WT) but not in the muscle-specific LKB1KO mice. Likewise, phosphorylation of acetyl-CoA carboxylase (ACC) was markedly attenuated in the KO mice. The LKB1KO mice had difficulty running on the treadmill and exhibited marked reduction in distance run in voluntary running wheels over a 3-wk period (5.9 +/- 0.9 km/day for WT vs. 1.7 +/- 0.7 km/day for MLKB1KO mice). The MLKB1KO mice anesthetized at rest exhibited significantly decreased phospho-AMPK and phospho-ACC compared with WT mice. KO mice exhibited lower levels of mitochondrial protein expression in the red and white regions of the quadriceps. These observations, along with previous observations from other laboratories, clearly demonstrate that LKB1 is the major upstream kinase in skeletal muscle and that it is essential for maintaining mitochondrial marker proteins in skeletal muscle. These data provide evidence for a critical role of LKB1 in muscle physiology, one of which is maintaining basal levels of mitochondrial oxidative enzymes. Capacity for voluntary running is compromised with muscle and heart LKB1 deficiency.


Subject(s)
Mitochondria, Muscle/enzymology , Muscle, Skeletal/metabolism , Myocardium/metabolism , Protein Serine-Threonine Kinases/metabolism , Running , AMP-Activated Protein Kinases , Acetyl-CoA Carboxylase/metabolism , Animals , Biomarkers/metabolism , Citrate (si)-Synthase/metabolism , Cytochromes c/metabolism , Glucose Transporter Type 4/metabolism , Hexokinase/metabolism , Mice , Mice, Knockout , Multienzyme Complexes/metabolism , Organ Specificity , Protein Serine-Threonine Kinases/genetics , Quadriceps Muscle/metabolism
17.
Organogenesis ; 2(1): 22-7, 2005 Jan.
Article in English | MEDLINE | ID: mdl-19521525

ABSTRACT

Neurogenin 3 (ngn3) is a basic helix loop helix transcription factor that is transiently expressed in the developing mouse pancreas with peak expression around E15. In mice lacking the ngn3 gene the endocrine cells of the pancreas fail to develop suggesting that the ngn3-positive cell may represent a progenitor cell for the endocrine pancreas. In order to purify and characterize this cell in detail we have generated a transgenic mouse, in which the ngn3 promoter drives expression of enhanced green fluorescent protein (EGFP). In the E15.5 embryo EGFP was expressed in the dorsal and ventral pancreas, the duodenum, and lower intestine as well as in the brain. This pattern of expression was in keeping with the known expression profile of the endogenous ngn3 gene. Within the pancreas EGFP was localized in close proximity to cells that stained positive for ngn3, insulin, and glucagon, but was absent from regions of the pancreas that stained positive for amylase. EGFP was also present in the pancreas at E18.5, although there was no detectable expression of ngn3. At this stage EGFP did not colocalize with any of the hormones or exocrine markers. EGFP(+) cells were FACS purified (96%) from the E15 pancreas yielding approximately 10,000 cells or 1.6% of the total pancreatic cells from one litter. RT/PCR analysis confirmed that the purified cells expressed EGFP, ngn3, insulin, glucagon, somatostatin and pancreatic polypeptide. The ability to purify ngn3(+) cells provides an invaluable source of material for charactering in detail their properties.

18.
Mycorrhiza ; 13(5): 239-47, 2003 Oct.
Article in English | MEDLINE | ID: mdl-14593517

ABSTRACT

Native grasses of semi-arid rangelands of the southwestern USA are more extensively colonized by dark septate endophytes (DSE) than by traditional mycorrhizal fungi. Roots of dominant grasses ( Bouteloua sp.) native to arid southwestern USA rangelands were prepared and stained using stains specific for fungi (trypan blue) and for lipids (sudan IV). This revealed extensive internal colonization of physiologically active roots by atypical fungal structures that appear to function as protoplasts, without a distinguishable wall or with very thin hyaline walls that escape detection by methods staining specifically for fungal chitin. These structures were presumed to be active fungal stages that progressed to form stained or melanized septate hyphae and microsclerotia characteristic of DSE fungi within dormant roots. The most conspicuous characteristic of these fungi were the unique associations that formed within sieve elements and the accumulation of massive quantities of lipids. This interface suggests a biologically significant location for carbon transfer between the plant and fungus. The continuous intimate association with all sieve elements, cortical and epidermal cells as well as external extension on the root surface and into the soil indicates that they are systemic and considerably more prevalent than previously thought. A fungal network associated with a mucilaginous complex observed on the root surface and its potential role in root function in dry soil is discussed. It is suggested that those fungi that non-pathogenically and totally colonize plant cells be classed as systemic endophytic fungi (SEF). This would refine the broad designation of DSE fungi. The potential mutualistic benefit of SEF for native plants in arid ecosystems based on the extent of lipid accumulation and its apparent distribution is discussed.


Subject(s)
Mycorrhizae/physiology , Plant Roots/microbiology , Poaceae/microbiology , Desert Climate , Mycorrhizae/ultrastructure , Plant Roots/physiology
19.
Article in English | MEDLINE | ID: mdl-15317290

ABSTRACT

The thrombin receptor on human platelets is the first member identified of a new family of G-protein coupled receptors referred to as protease activated receptors (PARs). These receptors are activated by a unique mechanism involving proteolytic cleavage of a portion of the extracellular domain to generate a new N-terminus which then acts as a tethered or intramolecular ligand (agonist) for the receptor. The hexapeptide SFLLRN-NH2 comprising the new N-terminus is referred to as the Thrombin Receptor Activating Peptide, or "TRAP" Thrombin is the most potent agonist for platelet aggregation and selective blockade of the intramolecular activation step without effecting the proteolytic activity of thrombin should result in moderation of platelet activation and aggregation without interfering with the other coagulation cascade effects of thrombin. Screening of combinatorial libraries identified a novel, non-peptide PAR-1 thrombin receptor antagonist. Examination of structure-activity relationships revealed that portions of the molecule could be replaced resulting in simpler molecules of lower molecular weight that were at the same time more potent. Molecules in this series were effective antagonists of TRAP-stimulated platelet activation, but had limited activity when thrombin was the agonist. Additional directed screening and subsequent lead refinement resulted in a second series of isoxazole based compounds. Some of the resultant molecules were potent PAR-1 antagonists that were effective against both TRAP- and thrombin-stimulated receptor activation. These compounds do not inhibit the proteolytic effects of thrombin but rather interfere with the intramolecular binding of the tethered ligand (SFLLRN) to the transmembrane portion of the thrombin receptor. They represent promising leads for future explorations of antithrombotic activity of thrombin receptor antagonists.


Subject(s)
Isoxazoles/pharmacology , Receptor, PAR-1/antagonists & inhibitors , Urea/analogs & derivatives , Urea/pharmacology , Blood Platelets/drug effects , Humans , Inhibitory Concentration 50 , Isoxazoles/chemistry , Platelet Aggregation Inhibitors/chemistry , Platelet Aggregation Inhibitors/pharmacology , Structure-Activity Relationship , Urea/chemistry
20.
Electrophoresis ; 22(18): 3939-48, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11700724

ABSTRACT

Single photon burst techniques were used to detect double-stranded DNA molecules in poly(methylmethacrylate) (PM MA) and polycarbonate (PC) microfluidic devices. A confocal epi-illumination detection system was constructed to monitor the fluorescence signature from single DNA molecules that were multiply labeled with the mono-intercalating dye, TOPRO-5, which possessed an absorption maximum at 765 nm allowing excitation with a solid-state diode laser and fluorescence monitoring in the near-infrared (IR). Near-IR excitation minimized autofluorescence produced from the polymer substrate, which was found to be significantly greater when excitation was provided in the visible range (488 nm). A solution containing lambda-DNA (48.5 kbp) was electrokinetically transported through the microfluidic devices at different applied voltages and solution pH values to investigate the effects of polymer substrate on the transport rate and detection efficiency of single molecular events. By applying an autocorrelation analysis to the data, we were able to obtain the molecular transit time of the individual molecules as they passed through the 7 microm laser beam. It was observed that the applied voltage for both devices affected the transport rate. However, solution pH did not alter the transit time for PM MA-based devices since the electroosmotic flow of PMMA was independent of solution pH. In addition, efforts were directed toward optimizing the sampling efficiency (number of molecules passing through the probe volume) by using either hydrodynamically focused flows from a sheath generated by electrokinetic pumping from side channels or reducing the channel width of the microfluidic device. Due to the low electroosmotic flows generated by both PMMA and PC, tight focusing of the sample stream was not possible. However, in PMMA devices, flow gating was observed by applying field strengths > -120 V/cm to the sheath flow channels. By narrowing the microchannel width, the number of molecular events detected per unit time was found to be four times higher in channels with 10 microm widths compared to those of 50 microm, indicating improved sampling efficiency for the narrower channels without significantly deteriorating detection efficiency. Attempts were made to do single molecule sizing of lambda-DNA, M13 (7.2 kbp) and pUC19 (2.7 kbp) using photon burst detection. While the average number of photons for each DNA type were different, the standard deviations were large due to the Gaussian intensity profile of the excitation beam. To demonstrate the sensitivity of single molecule analysis in the near-IR using polymer microfluidic devices, the near-IR chromophore, NN382, wasanalyzed using ourconfocal imager. A detection efficiency of 94% for single NN382 molecules was observed in the PC devices.


Subject(s)
DNA, Viral/analysis , Electrophoresis, Capillary/instrumentation , Fluorometry/instrumentation , Microchemistry/instrumentation , Polycarboxylate Cement/chemistry , Polymethyl Methacrylate/chemistry , Bacteriophage lambda/chemistry , Equipment Design , Fluorescent Dyes/analysis , Fluorescent Dyes/chemistry , Intercalating Agents/analysis , Intercalating Agents/chemistry , Lasers , Molecular Weight , Quinolines/analysis , Quinolines/chemistry , Rheology , Sensitivity and Specificity , Thiazoles/analysis , Thiazoles/chemistry , Time Factors
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