Interactions between a single emitter and cavity provide the archetypical system for fundamental quantum electrodynamics. Here we show that a single molecule of Atto647 aligned using DNA origami ...interacts coherently with a sub-wavelength plasmonic nanocavity, approaching the cooperative regime even at room temperature. Power-dependent pulsed excitation reveals Rabi oscillations, arising from the coupling of the oscillating electric field between the ground and excited states. The observed single-molecule fluorescent emission is split into two modes resulting from anti-crossing with the plasmonic mode, indicating the molecule is strongly coupled to the cavity. The second-order correlation function of the photon emission statistics is found to be pump wavelength dependent, varying from g
(0) = 0.4 to 1.45, highlighting the influence of vibrational relaxation on the Jaynes-Cummings ladder. Our results show that cavity quantum electrodynamic effects can be observed in molecular systems at ambient conditions, opening significant potential for device applications.
A series of fluorinated bis(aryl)platinum(II) complexes, cis-Pt(Ar(f))2(1,5-C6H10) (Ar(f) = p-C6HF4, p-C6(OMe)F4 or C6H2F(3-)2,4,6) were reacted with the four-membered gallium(I) or indium(I) ...heterocycles, :E{N(Ar)2CN(C6H11)2} (E = Ga or In, Ar = C6H3Pr(i)(2-)2,6) under various stoichiometries. These yielded either the 2:1 complexes, cis-Pt(Ar(f))2{Ga{N(Ar)2CN(C6H11)2}}2, trans-Pt(C6H2F(3-)2,4,6)2{Ga{N(Ar)2CN(C6H11)2}}2 and trans-Pt(Ar(f))2{In{N(Ar)2CN(C6H11)2}}2, or the 3:1 complexes, trans-Pt(Ar(f))2{In{N(Ar)2CN(C6H11)2}}3 (Ar(f) = p-C6HF4 or p-C6(OMe)F4), all of which were crystallographically characterised. The differing outcomes of these reactions are explained in terms of the lesser nucleophilicity and greater electrophilicity of the indium heterocycle relative to its gallium counterpart. In the solid state, and in solution, the 3:1 indium complexes exhibit strong intramolecular In...F interactions which are indicative of their heterocyclic ligands displaying rare examples of "Lewis amphoteric" behaviour. An unusual platinum(0) complex in which the indium(I) heterocycle acts as a mu3-bridging ligand, {Pt(norbornene)}3{mu3-In{N(Ar)2CN(C6H11)2}}2, was also prepared and structurally authenticated.
OBJECTIVE:To assess the efficacy and safety of eslicarbazepine acetate (ESL) monotherapy.
METHODS:This post hoc pooled analysis of 2 randomized double-blind studies (093-045 and -046) included adults ...with partial-onset seizures medically uncontrolled by 1 or 2 antiepileptic drugs (AEDs). Following the baseline period (8 weeks), eligible patients were randomized 2:1 to receive ESL 1,600 mg or 1,200 mg once daily for 18 weeks; the primary endpoint was study exit by meeting predefined exit criteria (signifying worsening seizure control). In each study, treatment was considered effective if the upper 95% confidence limit for exit rate was lower than the historical control threshold (65.3%).
RESULTS:Pooled exit rates were as followsESL 1,600 mg = 20.6% (95% confidence interval15.6%–26.8%); ESL 1,200 mg = 30.8% (23.0%–40.5%). Use of 2 baseline AEDs or rescue medication, US location, epilepsy duration ≥20 years, and higher maximum baseline seizure frequency were associated with higher exit risks. Median percent reductions in standardized seizure frequency between baseline and the 18-week double-blind period were as followsESL 1,600 mg = 43.2%; ESL 1,200 mg = 35.7%; baseline carbamazepine use was associated with smaller reductions. Safety profiles were similar between ESL doses.
CONCLUSIONS:Exit rates for ESL monotherapy (1,600 mg and 1,200 mg once daily) were lower than the historical control threshold, irrespective of baseline AED use and region, with no additional safety concerns identified. Clinical factors and location clearly influence treatment responses in conversion-to-monotherapy trials.
CLASSIFICATION OF EVIDENCE:This pooled analysis provides Class IV evidence that for adults with medically uncontrolled partial-onset seizures, ESL monotherapy is well tolerated and effective.
Only three elements are ferromagnetic at room temperature: the transition metals iron, cobalt and nickel. The Stoner criterion explains why iron is ferromagnetic but manganese, for example, is not, ...even though both elements have an unfilled 3d shell and are adjacent in the periodic table: according to this criterion, the product of the density of states and the exchange integral must be greater than unity for spontaneous spin ordering to emerge. Here we demonstrate that it is possible to alter the electronic states of non-ferromagnetic materials, such as diamagnetic copper and paramagnetic manganese, to overcome the Stoner criterion and make them ferromagnetic at room temperature. This effect is achieved via interfaces between metallic thin films and C60 molecular layers. The emergent ferromagnetic state exists over several layers of the metal before being quenched at large sample thicknesses by the material's bulk properties. Although the induced magnetization is easily measurable by magnetometry, low-energy muon spin spectroscopy provides insight into its distribution by studying the depolarization process of low-energy muons implanted in the sample. This technique indicates localized spin-ordered states at, and close to, the metal-molecule interface. Density functional theory simulations suggest a mechanism based on magnetic hardening of the metal atoms, owing to electron transfer. This mechanism might allow for the exploitation of molecular coupling to design magnetic metamaterials using abundant, non-toxic components such as organic semiconductors. Charge transfer at molecular interfaces may thus be used to control spin polarization or magnetization, with consequences for the design of devices for electronic, power or computing applications (see, for example, refs 6 and 7).
Whole-genome genetic association studies in outbred mouse populations represent a novel approach to identifying the molecular basis of naturally occurring genetic variants, the major source of ...quantitative variation between inbred strains of mice. Measuring multiple phenotypes in parallel on each mouse would make the approach cost effective, but protocols for phenotyping on a large enough scale have not been developed. In this article we describe the development and deployment of a protocol to collect measures on three models of human disease (anxiety, type II diabetes, and asthma) as well as measures of mouse blood biochemistry, immunology, and hematology. We report that the protocol delivers highly significant differences among the eight inbred strains (A/J, AKR/J, BALBc/J, CBA/J, C3H/HeJ, C57BL/6 J, DBA/2 J, and LP/J), the progenitors of a genetically heterogeneous stock (HS) of mice. We report the successful collection of multiple phenotypes from 2000 outbred HS animals. The phenotypes measured in the protocol form the basis of a large-scale investigation into the genetic basis of complex traits in mice designed to examine interactions between genes and between genes and environment, as well as the main effects of genetic variants on phenotypes.
A phase II trial was performed to test whether systemic low-dose interleukin-2 (IL-2) augments T-cell immune responses to a multipeptide melanoma vaccine. Forty patients with resected stage IIB-IV ...melanoma were randomly assigned to vaccination with four gp100- and tyrosinase-derived peptides restricted by human leukocyte antigen (HLA) -A1, HLA-A2, and HLA-A3, and a tetanus helper peptide plus IL-2 administered daily either beginning day 7 (group 1), or beginning day 28 (group 2).
T-cell responses were assessed by an interferon gamma ELIspot assay in peripheral blood lymphocytes (PBL) and in a lymph node draining a vaccination site (sentinel immunized node SIN). Patients were followed for disease-free and overall survival.
T-cell responses to the melanoma peptides were observed in 37% of PBL and 38% of SINs in group 1, and in 53% of PBL and 83% of SINs in group 2. The magnitude of T-cell response was higher in group 2. The tyrosinase peptides DAEKSDICTDEY and YMDGTMSQV were more immunogenic than the gp100 peptides YLEPGPVTA and ALLAVGATK. T-cell responses were detected in the SINs more frequently, and with higher magnitude, than responses in the PBL. Disease-free survival estimates at 2 years were 39% (95% CI, 18% to 61%) for group 1, and 50% (95% CI, 28% to 72%) for group 2 (P = .32).
The results of this study support the safety and immunogenicity of a vaccine composed of four peptides derived from gp100 and tyrosinase. The low-dose IL-2 regimen used for group 1 paradoxically diminishes the magnitude and frequency of cytotoxic T lymphocyte responses to these peptides.
Mutations in the BRCA1 and BRCA2 genes are found in most families with cases of both breast and ovarian cancer or with many cases of early-onset breast cancer. However, in an outbred population, the ...prevalence of BRCA1 and BRCA2 mutations in patients with breast cancer who were unselected for a family history of this disease has not been determined.
Mutations in the BRCA1 and BRCA2 genes were detected in blood samples from two population-based series of young patients with breast cancer from Britain.
Mutations were detected in 15 (5.9%) of 254 women diagnosed with breast cancer before age 36 years (nine 3.5% in BRCA1 and six 2.4% in BRCA2) and in 15 (4.1%) of 363 women diagnosed from ages 36 through 45 years (seven 1.9% in BRCA1 and eight 2.2% in BRCA2). Eleven percent (six of 55) of patients with a first-degree relative who developed ovarian cancer or breast cancer by age 60 years were mutation carriers, compared with 45% (five of 11) of patients with two or more affected first- or second-degree relatives. The standardized incidence ratio for breast cancer in mothers and sisters was 365 (five observed and 1.37 expected) for 30 mutation carriers and 199 (64 observed and 32.13 expected) for 587 noncarriers. If we assume recent penetrance estimates, the respective proportions of BRCA1 and BRCA2 mutation carriers are 3.1% and 3.0%, respectively, of patients with breast cancer who are younger than age 50 years, 0.49% and 0.84% of patients with breast cancer who are age 50 years or older, and 0.11% and 0.12% of women in the general population.
Mutations in the BRCA1 and BRCA2 genes make approximately equal contributions to early-onset breast cancer in Britain and account for a small proportion of the familial risk of breast cancer.
Ultra‐Broadband, High Efficiency Polarized Beam Splitter Metagrating
In article number 2201227, Hui‐Hsin Hsiao, Richard E. Muller, Dejian Fu, and co‐workers demonstrate a polarized beam splitter ...metagrating that enables simultaneous measurement of four spatialspectral‐ polarimetric images with an efficiency of 70% and a polarimetric contrast greater than 0.996 in the entire near‐infrared oxygen bands, which will be integrated into NASA's high‐resolution multiplespecies atmospheric profiler instrument for vertical profiling of global aerosols.
A broadband, high efficiency polarized beam splitter (PBS) metagrating based on integrated resonant units (IRUs) to enable simultaneous polarization analysis, spectral dispersion, and spatial imaging ...in the near infrared (NIR) is developed. A PBS metagrating with a diameter of 60 mm is the key technology component of the high‐resolution multiple‐species atmospheric profiler in the NIR (HiMAP‐NIR), which is a spaceborne instrument concept crafted to be a core payload of NASA's new generation Earth System Observatory. HiMAP‐NIR will enable the aerosol profiling in Earth's planetary boundary layer (from surface to2 km altitude) by simultaneously measuring four spatial‐spectral‐polarimetric images from 680 to 780 nm. Through detailed optimization of hybridized resonant modes in IRUs, the PBS metagrating shows a diffraction efficiency of 70% (or better) for all four linear‐polarized incident light, and polarization contrasts between orthogonal states are 0.996 (or better) from 680 to 780 nm. It meets the stringent performance required by the HiMAP‐NIR exploiting a new paradigm for the broad applications of metasurfaces.
An polarized beam splitter, enabling to simultaneously measure four spatial‐spectral‐polarimetric images with an efficiency ≈70% in the entire near‐infrared oxygen bands and a polarization contrast greater than 0.996, are realized by hybridized gap‐plasmonic metasurfaces. This meets the standard of NASA's high‐resolution multiple‐species atmospheric profiler instrument for aerosol profiling in the planetary boundary layer.
To determine clinical and immunologic responses to a multipeptide melanoma vaccine regimen, a randomized phase II trial was performed.
Twenty-six patients with advanced melanoma were randomly ...assigned to vaccination with a mixture of four gp100 and tyrosinase peptides restricted by HLA-A1, HLA-A2, and HLA-A3, plus a tetanus helper peptide, either in an emulsion with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Montanide ISA-51 adjuvant (Seppic Inc, Fairfield, NJ), or pulsed on monocyte-derived dendritic cells (DCs). Systemic low-dose interleukin-2 (Chiron, Emeryville, CA) was given to both groups. T-lymphocyte responses were assessed, by interferon gamma ELIspot assay (Chiron, Emeryville, CA), in peripheral-blood lymphocytes (PBLs) and in a lymph node draining a vaccine site (sentinel immunized node SIN).
In patients vaccinated with GM-CSF in adjuvant, T-cell responses to melanoma peptides were observed in 42% of PBLs and 80% of SINs, but in patients vaccinated with DCs, they were observed in only 11% and 13%, respectively. The overall immune response was greater in the GM-CSF arm (P <.02). Vitiligo developed in two of 13 patients in the GM-CSF arm but in no patients in the DC arm. Helper T-cell responses to the tetanus peptide were detected in PBLs after vaccination and correlated with T-cell reactivity to the melanoma peptides. Objective clinical responses were observed in two patients in the GM-CSF arm and one patient in the DC arm. Stable disease was observed in two patients in the GM-CSF arm and one patient in the DC arm.
The high frequency of cytotoxic T-lymphocyte responses and the occurrence of clinical tumor regressions support continued investigation of multipeptide vaccines administered with GM-CSF in adjuvant.
PDF
