879 research outputs found
A method for concentrating lipid peptide DNA and siRNA nanocomplexes that retains their structure and transfection efficiency
Nonviral gene and small interfering RNA (siRNA) delivery formulations are extensively used for biological and therapeutic research in cell culture experiments, but less so in in vivo and clinical research. Difficulties with formulating the nanoparticles for uniformity and stability at concentrations required for in vivo and clinical use are limiting their progression in these areas. Here, we report a simple but effective method of formulating monodisperse nanocomplexes from a ternary formulation of lipids, targeting peptides, and nucleic acids at a low starting concentration of 0.2 mg/mL of DNA, and we then increase their concentration up to 4.5 mg/mL by reverse dialysis against a concentrated polymer solution at room temperature. The nanocomplexes did not aggregate and they had maintained their biophysical properties, but, importantly, they also mediated DNA transfection and siRNA silencing in cultured cells. Moreover, concentrated anionic nanocomplexes administered by convection-enhanced delivery in the striatum showed efficient silencing of the ÎČ-secretase gene BACE1. This method of preparing nanocomplexes could probably be used to concentrate other nonviral formulations and may enable more widespread use of nanoparticles in vivo
High School Exit Examinations: When Do Learning Effects Generalize?
This paper reviews international and domestic evidence on the effects of three types of high school exit exam systems: voluntary curriculum-based external exit exams, universal curriculum-based external exit exam systems and minimum competency tests that must be passed to receive a regular high school diploma. The nations and provinces that use Universal CBEEES (and typically teacher grades as well) to signal student achievement have significantly higher achievement levels and smaller differentials by family background than otherwise comparable jurisdictions that base high stakes decisions on voluntary college admissions tests and/or teacher grades. The introduction of Universal CBEEES in New York and North Carolina during the 1990s was associated with large increases in math achievement on NAEP tests. Research on MCTs and high school accountability tests is less conclusive because these systems are new and have only been implemented in one country. Cross-section studies using a comprehensive set of controls for family background have not found that students in MCT states score higher on audit tests like the NAEP that carry no stakes for the test taker. The analysis reported in table 1 tells us that the five states that introduced MCTs during the 1990s had significantly larger improvements on NAEP tests than states that made no change in their student accountability regime. The gains, however, are smaller than for the states introducing Universal CBEEES. New York and North Carolina. The most positive finding about MCTs is that students in MCT states earn significantly more during the first eight years after graduation than comparable students in other states suggesting that MCTs improve employer perceptions of the quality of the recent graduates of local high schools
The effects of cold working on sensitization and intergranular corrosion behavior of AISI 304 stainless steel
The effects of prior cold rolling of up to an 80 pct reduction in thickness on the sensitization-desensitization behavior of Type AISI 304 stainless steel and its susceptibility to intergranular corrosion have been studied by electrochemical potentiokinetic reactivation (EPR) and Strauss-test methods. The results indicate that the prior deformation accelerated the sensitization as compared to the undeformed stainless steel. The deformed Type 304 stainless steel experienced desensitization at higher temperatures and times, and it was found to be enhanced by increased cold deformation. This could be attributed to the increased long-range chromium diffusion, possibly brought on by increasing pipe diffusion and vacancies. The role of the deformation-induced martensite (DIM) and texture, introduced by uniaxial cold rolling, on the sensitization-desensitization kinetics has also been discussed. This study could not reveal any systematic relationship between texture and the degree of sensitization (DOS) obtained. The effect of DIM on DOS seems to be pronounced at 500 °C when the steel retained significant amounts of DIM; however, the retained DIM is insignificant at higher sensitization times and temperatures
On topological charge carried by nexuses and center vortices
In this paper we further explore the question of topological charge in the
center vortex-nexus picture of gauge theories. Generally, this charge is
locally fractionalized in units of 1/N for gauge group SU(N), but globally
quantized in integral units. We show explicitly that in d=4 global topological
charge is a linkage number of the closed two-surface of a center vortex with a
nexus world line, and relate this linkage to the Hopf fibration, with homotopy
; this homotopy insures integrality of the global
topological charge. We show that a standard nexus form used earlier, when
linked to a center vortex, gives rise naturally to a homotopy , a homotopy usually associated with 't Hooft-Polyakov monopoles and similar
objects which exist by virtue of the presence of an adjoint scalar field which
gives rise to spontaneous symmetry breaking. We show that certain integrals
related to monopole or topological charge in gauge theories with adjoint
scalars also appear in the center vortex-nexus picture, but with a different
physical interpretation. We find a new type of nexus which can carry
topological charge by linking to vortices or carry d=3 Chern-Simons number
without center vortices present; the Chern-Simons number is connected with
twisting and writhing of field lines, as the author had suggested earlier. In
general, no topological charge in d=4 arises from these specific static
configurations, since the charge is the difference of two (equal) Chern-Simons
number, but it can arise through dynamic reconnection processes. We complete
earlier vortex-nexus work to show explicitly how to express globally-integral
topological charge as composed of essentially independent units of charge 1/N.Comment: Revtex4; 3 .eps figures; 18 page
Local Ultrasound-Facilitated Thrombolysis in High-Risk Pulmonary Embolism: First Dutch Experience
Purpose To provide insight into the current use and results
of ultrasound-facilitated catheter-directed thrombolysis
(USAT) in patients with high-risk pulmonary embolism
(PE).
Introduction Systemic thrombolysis is an effective treatment for hemodynamically unstable, high-risk PE, but is
associated with bleeding complications. USAT is thought
to reduce bleeding and is therefore advocated in patients
with high-risk PE and contraindications for systemic
thrombolysis.
Methods We conducted a retrospective cohort study of all
patients who underwent USAT for high-risk PE in the
Netherlands from 2010 to 2017. Characteristics and outcomes were analyzed. Primary outcomes were major
(including intracranial and fatal) bleeding and all-cause
mortality after 1 month. Secondary outcomes were allcause mortality and recurrent venous thromboembolism
within 3 months.
Results 33 patients underwent USAT for high-risk PE.
Major bleeding occurred in 12 patients (36%, 95% CI
22â53), including 1 intracranial and 3 fatal bleeding. Allcause mortality after 1 month was 48% (16/33, 95% CI
31â66). All-cause mortality after 3 months was 50% (16/
32, 95% CI 34â66), recurrent venous thromboembolism
occurred in 1 patient (1/32, 3%, 95% CI 1â16).
Conclusions This study was the first to describe characteristics and outcomes after USAT in a study population of
patients with high-risk PE only, an understudied population. Although USAT is considered a relatively safe
treatment option, our results illustrate that at least caution
is needed in critically ill patients with high-risk PE. Further
research in patients with high-risk PE is warranted to guide
patient selection
Long-term exposures to air pollution and the risk of atrial fibrillation in the womenâs health initiative cohort
BACKGROUND: Atrial fibrillation (AF) is associated with substantial morbidity and mortality. Short-term exposures to air pollution have been associated with AF triggering; less is known regarding associations between long-term air pollution exposures and AF incidence. OBJECTIVES: Our objective was to assess the association between long-term exposures to air pollution and distance to road on incidence of AF in a cohort of U.S. women. METHODS: We assessed the association of high resolution spatiotemporal model predictions of long-term exposures to particulate matter (PM10 and PM2:5 ), sulfur dioxide (SO2 ), nitrogen dioxide (NO2 ), and distance to major roads with incidence of AF diagnosis, identified through Medicare link-age, among 83,117 women in the prospective Womenâs Health Initiative cohort, followed from enrollment in Medicare through December 2012, incidence of AF, or death. Using time-varying Cox proportional hazards models adjusted for age, race/ethnicity, study component, body mass index, physical activity, menopausal hormone therapy, smoking, diet quality, alcohol consumption, educational attainment, and neighborhood socioeconomic status, we estimated the relative risk of incident AF in association with each pollutant. RESULTS: A total of 16,348 incident AF cases were observed over 660,236 person-years of follow-up. Most exposureâresponse associations were non-linear. NO2 was associated with risk of AF in multivariable adjusted models [Hazard Ratio Ă°HRĂ = 1:18; 95% confidence interval (CI): 1.13, 1.24, comparing the top to bottom quartile, p-for-trend = < 0:0001]. Women living closer to roadways were at higher risk of AF (e.g., HR = 1:07; 95% CI: 1.01, 1.13 for living within 50 m of A3 roads, compared with â„1,000 m, p-for-trend = 0:02), but we did not observe adverse associations with exposures to PM10, PM2:5, or SO2 . There were adverse associations with PM10 (top quartile HR = 1:10; 95% CI: 1.05, 1.16, p-for-trend = < 0:0001) and PM2:5 (top quartile HR = 1:09; 95% CI: 1.03, 1.14, p-for-trend = 0:002) in sensitivity models adjusting for census region. DISCUSSION: In this study of postmenopausal women, NO2 and distance to road were consistently associated with higher risk of AF. https://doi.org/10.1289/EHP7683
Search for lepton-flavor violation at HERA
A search for lepton-flavor-violating interactions and has been performed with the ZEUS detector using the entire HERA I
data sample, corresponding to an integrated luminosity of 130 pb^{-1}. The data
were taken at center-of-mass energies, , of 300 and 318 GeV. No
evidence of lepton-flavor violation was found, and constraints were derived on
leptoquarks (LQs) that could mediate such interactions. For LQ masses below
, limits were set on , where
is the coupling of the LQ to an electron and a
first-generation quark , and is the branching ratio of
the LQ to the final-state lepton ( or ) and a quark . For
LQ masses much larger than , limits were set on the four-fermion
interaction term for LQs that couple to an electron and a quark
and to a lepton and a quark , where and are
quark generation indices. Some of the limits are also applicable to
lepton-flavor-violating processes mediated by squarks in -Parity-violating
supersymmetric models. In some cases, especially when a higher-generation quark
is involved and for the process , the ZEUS limits are the most
stringent to date.Comment: 37 pages, 10 figures, Accepted by EPJC. References and 1 figure (Fig.
6) adde
Multijet production in neutral current deep inelastic scattering at HERA and determination of alpha_s
Multijet production rates in neutral current deep inelastic scattering have
been measured in the range of exchanged boson virtualities 10 < Q2 < 5000 GeV2.
The data were taken at the ep collider HERA with centre-of-mass energy sqrt(s)
= 318 GeV using the ZEUS detector and correspond to an integrated luminosity of
82.2 pb-1. Jets were identified in the Breit frame using the k_T cluster
algorithm in the longitudinally invariant inclusive mode. Measurements of
differential dijet and trijet cross sections are presented as functions of jet
transverse energy E_{T,B}{jet}, pseudorapidity eta_{LAB}{jet} and Q2 with
E_{T,B}{jet} > 5 GeV and -1 < eta_{LAB}{jet} < 2.5. Next-to-leading-order QCD
calculations describe the data well. The value of the strong coupling constant
alpha_s(M_Z), determined from the ratio of the trijet to dijet cross sections,
is alpha_s(M_Z) = 0.1179 pm 0.0013(stat.) {+0.0028}_{-0.0046}(exp.)
{+0.0064}_{-0.0046}(th.)Comment: 22 pages, 5 figure
Photoproduction of mesons associated with a leading neutron
The photoproduction of mesons associated with a leading
neutron has been observed with the ZEUS detector in collisions at HERA
using an integrated luminosity of 80 pb. The neutron carries a large
fraction, {}, of the incoming proton beam energy and is detected at
very small production angles, { mrad}, an indication of
peripheral scattering. The meson is centrally produced with
pseudorapidity {
GeV}, which is large compared to the average transverse momentum of the neutron
of 0.22 GeV. The ratio of neutron-tagged to inclusive production is
in the photon-proton
center-of-mass energy range { GeV}. The data suggest that the
presence of a hard scale enhances the fraction of events with a leading neutron
in the final state.Comment: 28 pages, 4 figures, 2 table
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