To assess the short-term safety and efficacy of treating subfoveal choroidal neovascularization (CNV) with external beam radiation delivered in 5 × 4 Gy fractions among patients having age-related ...macular degeneration (AMD).
A multicenter prospective randomized controlled pilot study.
Eighty-eight patients were enrolled through 10 sites and were randomized to radiotherapy (20 Gy delivered in 5 daily fractions of 4 Gy each; 6 MV N = 41) or no radiotherapy (sham radiotherapy N = 22 or observation N = 25). Eligibility criteria included visual acuity of at least 20/320 and subfoveal CNV not amenable to treatment. Randomization was stratified by lesion type (new or recurrent CNV) and blood (<50% or ≥50% of the lesion N = 13). The primary outcome measure was loss of ≥3 lines of visual acuity. Secondary outcome measures were angiographic response and side effects.
At baseline, patient and ocular characteristics were similar between treatment groups. At six months, 9 radiated eyes (26%) and 17 eyes not radiated (49%) lost ≥3 lines of visual acuity (
P = .04; stratified χ
2 test). At 12 months, 13 radiated eyes (42%) and 9 observed eyes (49%) lost ≥3 visual acuity lines (
P = .60). The radiated group demonstrated smaller lesions and less fibrosis than the nonradiated group (
P = .05 and .004, respectively) at 12 months. Radiation-induced complications were not observed except for one radiated eye with numerous cotton wool spots and possible radiation retinopathy.
External beam radiation at 5 × 4 Gy may have a modest and short-lived (six month) benefit in preserving visual acuity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
With accumulating evidence indicating the importance of cytotoxic T lymphocytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replication in infected individuals, strategies are being ...pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. Here, we report the protective efficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys. Immune responses were elicited by DNA vaccines expressing SIVmac239 Gag and HIV-1 89.6P Env, augmented by the administration of the purified fusion protein IL-2/Ig, consisting of interleukin-2 (IL-2) and the Fc portion of immunoglobulin G (IgG), or a plasmid encoding IL-2/Ig. After SHIV-89.6P infection, sham-vaccinated monkeys developed weak CTL responses, rapid loss of CD4+T cells, no virus-specific CD4+T cell responses, high setpoint viral loads, significant clinical disease progression, and death in half of the animals by day 140 after challenge. In contrast, all monkeys that received the DNA vaccines augmented with IL-2/Ig were infected, but demonstrated potent secondary CTL responses, stable CD4+T cell counts, preserved virus-specific CD4+T cell responses, low to undetectable setpoint viral loads, and no evidence of clinical disease or mortality by day 140 after challenge.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The maize genome is relatively large (∼2.3 Gb) and has a complex organization of interspersed genes and transposable elements, which necessitates frequent boundaries between different types of ...chromatin. The examination of maize genes and conserved noncoding sequences revealed that many of these are flanked by regions of elevated asymmetric CHH (where H is A, C, or T) methylation (termed mCHH islands). These mCHH islands are quite short (∼100 bp), are enriched near active genes, and often occur at the edge of the transposon that is located nearest to genes. The analysis of DNA methylation in other sequence contexts and several chromatin modifications revealed that mCHH islands mark the transition from heterochromatin-associated modifications to euchromatin-associated modifications. The presence of an mCHH island is fairly consistent in several distinct tissues that were surveyed but shows some variation among different haplotypes. The presence of insertion/deletions in promoters often influences the presence and position of an mCHH island. The mCHH islands are dependent upon RNA-directed DNA methylation activities and are lost inmop1andmop3mutants, but the nearby genes rarely exhibit altered expression levels. Instead, loss of an mCHH island is often accompanied by additional loss of DNA methylation in CG and CHG contexts associated with heterochromatin in nearby transposons. This suggests that mCHH islands and RNA-directed DNA methylation near maize genes may act to preserve the silencing of transposons from activity of nearby genes.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Staphylococcus aureus is thought to have acquired mecA DNA by horizontal transfer. DNA fingerprints made by restriction nucleases that cut certain sequences of DNA are used to compare complete ...genomes or particular genes between bacteria. We isolated an epidemic mecA
− meticillin-susceptible S aureus genotype and, subsequently, a rare isogeneic mecA
+ meticillin-resistant S aureus (MRSA) genotype from a neonate who had never been in contact with MRSA. This MRSA contained mecA DNA that was identical to that in a coagulase-negative staphylococcal strain isolated from this patient, but different from other MRSA genotypes. We believe that this MRSA was formed in vivo by horizontal transfer of the mecA DNA between two staphylococcal species.
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DOBA, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SIK, UILJ, UKNU, UL, UM, UPCLJ, UPUK, VSZLJ
Trafficking and biophysical properties of AMPA receptors (AMPARs) in the brain depend on interactions with associated proteins. We identify Shisa6, a single transmembrane protein, as a stable and ...directly interacting bona fide AMPAR auxiliary subunit. Shisa6 is enriched at hippocampal postsynaptic membranes and co-localizes with AMPARs. The Shisa6 C-terminus harbours a PDZ domain ligand that binds to PSD-95, constraining mobility of AMPARs in the plasma membrane and confining them to postsynaptic densities. Shisa6 expressed in HEK293 cells alters GluA1- and GluA2-mediated currents by prolonging decay times and decreasing the extent of AMPAR desensitization, while slowing the rate of recovery from desensitization. Using gene deletion, we show that Shisa6 increases rise and decay times of hippocampal CA1 miniature excitatory postsynaptic currents (mEPSCs). Shisa6-containing AMPARs show prominent sustained currents, indicating protection from full desensitization. Accordingly, Shisa6 prevents synaptically trapped AMPARs from depression at high-frequency synaptic transmission.
It has been observed in the literature that measurements of low-mass Drell–Yan (DY) transverse momentum spectra at low center-of-mass energies
s
are not well described by perturbative QCD ...calculations in collinear factorization in the region where transverse momenta are comparable with the DY mass. We examine this issue from the standpoint of the Parton Branching (PB) method, combining next-to-leading-order (NLO) calculations of the hard process with the evolution of transverse momentum dependent (TMD) parton distributions. We compare our predictions with experimental measurements at low DY mass, and find very good agreement. In addition we use the low mass DY measurements at low
s
to determine the width
q
s
of the intrinsic Gauss distribution of the PB-TMDs at low evolution scales. We find values close to what has earlier been used in applications of PB-TMDs to high-energy processes at the Large Hadron Collider (LHC) and HERA. We find that at low DY mass and low
s
even in the region of
p
T
/
m
DY
∼
1
the contribution of multiple soft gluon emissions (included in the PB-TMDs) is essential to describe the measurements, while at larger masses (
m
DY
∼
m
Z
) and LHC energies the contribution from soft gluons in the region of
p
T
/
m
DY
∼
1
is small.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
With its large acceptance and particle identification coverage the NA49 experiment (Fig. 1) can study hadron production in a wide range of high energy reactions 1. Originally aimed at examining ...central Pb+Pb collisions for signatures of quark-gluon plasma formation, the scope of the experiment has been enhanced with a systematic study of impact parameter and projectile size dependence, as well as the inclusion of the more elementary p+p and p+A interactions. The question is: are predicted signals of the quark-gluon plasma observed and are there discontinuities which would support the concept of hadronic phase transition?
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Predator effects on prey dynamics are conventionally studied by measuring changes in prey abundance attributed to consumption by predators. We revisit four classic examples of predator—prey systems ...often cited in textbooks and incorporate subsequent studies of nonconsumptive effects of predators (NCE), defined as changes in prey traits (e.g., behavior, growth, development) measured on an ecological time scale. Our review revealed that NCE were integral to explaining lynx—hare population dynamics in boreal forests, cascading effects of top predators in Wisconsin lakes, and cascading effects of killer whales and sea otters on kelp forests in nearshore marine habitats. The relatives roles of consumption and NCE of wolves on moose and consequent indirect effects on plant communities of Isle Royale depended on climate oscillations. Nonconsumptive effects have not been explicitly tested to explain the link between planktonic alewives and the size structure of the zooplankton, nor have they been invoked to attribute keystone predator status in intertidal communities or elsewhere. We argue that both consumption and intimidation contribute to the total effects of keystone predators, and that characteristics of keystone consumers may differ from those of predators having predominantly NCE. Nonconsumptive effects are often considered as an afterthought to explain observations inconsistent with consumption-based theory. Consequently, NCE with the same sign as consumptive effects may be overlooked, even though they can affect the magnitude, rate, or scale of a prey response to predation and can have important management or conservation implications. Nonconsumptive effects may underlie other classic paradigms in ecology, such as delayed density dependence and predator-mediated prey coexistence. Revisiting classic studies enriches our understanding of predator—prey dynamics and provides compelling rationale for ramping up efforts to consider how NCE affect traditional predator—prey models based on consumption, and to compare the relative magnitude of consumptive and NCE of predators.
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BFBNIB, FZAB, GIS, IJS, INZLJ, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZRSKP
We provide an updated version of the Compendium of Physical Activities, a coding scheme that classifies specific physical activity (PA) by rate of energy expenditure. It was developed to enhance the ...comparability of results across studies using self-reports of PA. The Compendium coding scheme links a five-digit code that describes physical activities by major headings (e.g., occupation, transportation, etc.) and specific activities within each major heading with its intensity, defined as the ratio of work metabolic rate to a standard resting metabolic rate (MET). Energy expenditure in MET-minutes, MET-hours, kcal, or kcal per kilogram body weight can be estimated for specific activities by type or MET intensity. Additions to the Compendium were obtained from studies describing daily PA patterns of adults and studies measuring the energy cost of specific physical activities in field settings. The updated version includes two new major headings of volunteer and religious activities, extends the number of specific activities from 477 to 605, and provides updated MET intensity levels for selected activities.
The ratio of cross sections for inelastic muon scattering on xenon and deuterium nuclei was measured at very low Bjorken {ital x} (0.000 02{lt}{ital x}{sub Bj}{lt}0.25). The data were taken at ...Fermilab experiment E-665 with a 490 GeV/{ital c} muon beam incident on liquid deuterium and gaseous xenon targets. Two largely independent analysis techniques gave statistically consistent results. The xenon-to-deterium per-nucleon cross-section ratio is constant at approximately 0.7 for {ital x}{sub Bj} below 0.003.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UM
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