Plasmon assisted transmission of high dimensional orbital angular momentum entangled state

We present an experimental evidence that high dimensional orbital angular momentum entanglement of a pair of photons can be survived after a photon-plasmon-photon conversion. The information of spatial modes can be coherently transmitted by surface plasmons. This experiment primarily studies the high dimensional entangled systems based on surface plasmon with subwavelength structures. It maybe useful in the investigation of spatial mode properties of surface plasmon assisted transmission through subwavelength hole arrays.Comment: 7 pages,6 figure

Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up.

PurposeIn the initial PALOMA-2 (NCT01740427) analysis with median follow-up of 23 months, palbociclib plus letrozole significantly prolonged progression-free survival (PFS) in women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) [hazard ratio (HR) 0.58; P < 0.001]. Herein, we report results overall and by subgroups with extended follow-up.MethodsIn this double-blind, phase 3 study, post-menopausal women with ER+/HER2- ABC who had not received prior systemic therapy for their advanced disease were randomized 2:1 to palbociclib-letrozole or placebo-letrozole. Endpoints include investigator-assessed PFS (primary), safety, and patient-reported outcomes (PROs).ResultsAfter a median follow-up of approximately 38 months, median PFS was 27.6 months for palbociclib-letrozole (n = 444) and 14.5 months for placebo-letrozole (n = 222) (HR 0.563; 1-sided P < 0.0001). All subgroups benefited from palbociclib treatment. The improvement of PFS with palbociclib-letrozole was maintained in the next 2 subsequent lines of therapy and delayed the use of chemotherapy (40.4 vs. 29.9 months for palbociclib-letrozole vs. placebo-letrozole). Safety data were consistent with the known profile. Patients' quality of life was maintained.ConclusionsWith approximately 15 months of additional follow-up, palbociclib plus letrozole continued to demonstrate improved PFS compared with placebo plus letrozole in the overall population and across all patient subgroups, while the safety profile remained favorable and quality of life was maintained. These data confirm that palbociclib-letrozole should be considered the standard of care for first-line therapy in patients with ER+/HER2- ABC, including those with low disease burden or long disease-free interval. Sponsored by Pfizer; ClinicalTrials.gov: NCT01740427

CrY2H-seq: a massively multiplexed assay for deep-coverage interactome mapping.

Broad-scale protein-protein interaction mapping is a major challenge given the cost, time, and sensitivity constraints of existing technologies. Here, we present a massively multiplexed yeast two-hybrid method, CrY2H-seq, which uses a Cre recombinase interaction reporter to intracellularly fuse the coding sequences of two interacting proteins and next-generation DNA sequencing to identify these interactions en masse. We applied CrY2H-seq to investigate sparsely annotated Arabidopsis thaliana transcription factors interactions. By performing ten independent screens testing a total of 36 million binary interaction combinations, and uncovering a network of 8,577 interactions among 1,453 transcription factors, we demonstrate CrY2H-seq's improved screening capacity, efficiency, and sensitivity over those of existing technologies. The deep-coverage network resource we call AtTFIN-1 recapitulates one-third of previously reported interactions derived from diverse methods, expands the number of known plant transcription factor interactions by three-fold, and reveals previously unknown family-specific interaction module associations with plant reproductive development, root architecture, and circadian coordination

Predictors of prolonged benefit from palbociclib plus fulvestrant in women with endocrine-resistant hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer in PALOMA-3

Abstract Background The addition of palbociclib to fulvestrant improved clinical outcomes over placebo-fulvestrant in endocrine-pretreated metastatic breast cancer (MBC) patients in PALOMA-3. Here, we examined factors predictive of long-term benefit. Methods Premenopausal-peri/postmenopausal patients with endocrine-resistant, hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative MBC were randomised 2:1 to fulvestrant (500 mg) and either palbociclib (125 mg/d; 3/1 schedule; n = 347) or placebo (n = 174). Baseline characteristics, mutation status and HR expression levels were compared in patients with and without prolonged benefit (treatment duration ≥18 months). Results By August 2016, 100 patients (29%) on palbociclib-fulvestrant and 26 (15%) on placebo-fulvestrant demonstrated prolonged benefit, with long-term responders in both arms sharing common clinical characteristics. They usually had less disease burden at baseline versus those treated Conclusions This exploratory analysis demonstrates that some patients with endocrine-resistant MBC derive significant and prolonged benefit when treated with palbociclib-fulvestrant, with fewer patients experiencing similar efficacy with placebo-fulvestrant. The current analysis did not identify specific molecular or clinical factors prognostic of long-term benefit with palbociclib-fulvestrant ( ClinicalTrials.gov , NCT01942135 )

Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer

BACKGROUND The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, prolongs progression-free survival among patients with hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer. We report the results of a prespecified analysis of overall survival. METHODS We randomly assigned patients with hormone-receptor–positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy to receive palbociclib plus fulvestrant or placebo plus fulvestrant. We analyzed overall survival; the effect of palbociclib according to the prespecified stratification factors of presence or absence of sensitivity to endocrine therapy, presence or absence of visceral metastatic disease, and menopausal status; the efficacy of subsequent therapies after disease progression; and safety. RESULTS Among 521 patients who underwent randomization, the median overall survival was 34.9 months (95% confidence interval [CI], 28.8 to 40.0) in the palbociclib– fulvestrant group and 28.0 months (95% CI, 23.6 to 34.6) in the placebo–fulvestrant group (hazard ratio for death, 0.81; 95% CI, 0.64 to 1.03; P=0.09; absolute difference, 6.9 months). CDK4/6 inhibitor treatment after the completion of the trial regimen occurred in 16% of the patients in the placebo–fulvestrant group. Among 410 patients with sensitivity to previous endocrine therapy, the median overall survival was 39.7 months (95% CI, 34.8 to 45.7) in the palbociclib–fulvestrant group and 29.7 months (95% CI, 23.8 to 37.9) in the placebo–fulvestrant group (hazard ratio, 0.72; 95% CI, 0.55 to 0.94; absolute difference, 10.0 months). The median duration of subsequent therapy was similar in the two groups, and the median time to the receipt of chemotherapy was 17.6 months in the palbociclib– fulvestrant group, as compared with 8.8 months in the placebo–fulvestrant group (hazard ratio, 0.58; 95% CI, 0.47 to 0.73; P<0.001). No new safety signals were observed with 44.8 months of follow-up. CONCLUSIONS Among patients with hormone-receptor–positive, HER2-negative advanced breast cancer who had sensitivity to previous endocrine therapy, treatment with palbociclib–fulvestrant resulted in longer overall survival than treatment with placebo– fulvestrant. The differences in overall survival in the entire trial group were not significant. (Funded by Pfizer; PALOMA-3 ClinicalTrials.gov number, NCT01942135.

Coherent spin qubit transport in silicon

A fault-tolerant quantum processor may be configured using stationary qubits interacting only with their nearest neighbours, but at the cost of significant overheads in physical qubits per logical qubit. Such overheads could be reduced by coherently transporting qubits across the chip, allowing connectivity beyond immediate neighbours. Here we demonstrate high-fidelity coherent transport of an electron spin qubit between quantum dots in isotopically-enriched silicon. We observe qubit precession in the inter-site tunnelling regime and assess the impact of qubit transport using Ramsey interferometry and quantum state tomography techniques. We report a polarization transfer fidelity of 99.97% and an average coherent transfer fidelity of 99.4%. Our results provide key elements for high-fidelity, on-chip quantum information distribution, as long envisaged, reinforcing the scaling prospects of silicon-based spin qubits

Associations Between Methylation of Paternally Expressed Gene 3 (PEG3), Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer.

Cytology-based screening for invasive cervical cancer (ICC) lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN) likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008-2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV) and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI 95%) for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2-2.1). HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7-48.6) and ICC (OR = 29.5, 95% CI 6.3-38.4). Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs) methylation (r = 0.34 p<0.0001), while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047). Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. Impact statement: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC), especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with a 1.6-fold increase ICC risk. Suggesting PEG3 methylation status may be useful as a molecular marker for CIN screening to improve prediction of cases likely to progress