Raman Laser Switching Induced by Cascaded Light Scattering

It is shown that, in multimode Raman lasers, cascaded light scattering (CLS) not only extends the optical frequency range, but can also modulate the laser dynamics. The origin of this phenomenon lies in the fact that many Raman lasing modes are directly correlated through CLS. The coupled‐mode equations only describe single‐mode cascaded Raman lasers and are insufficient for describing the multimode case. In this work, additional terms are introduced to account for intermodal interaction and, therefrom the physical mechanism behind the mode‐switching phenomenon is revealed. Additionally, mode‐switching controlled solely by a single‐mode pump in a whispering gallery mode (WGM) silica Raman laser is demonstrated. As the intracavity pump power is increased, laser switching happens between two adjacent WGMs in the same mode family

Rediscovery of the Threatened River Sharks, Glyphis garricki and G. glyphis, in Papua New Guinea

Recent surveys of the shark and ray catches of artisanal fishers in the Western Province of Papua New Guinea (PNG) resulted in the rediscovery of the threatened river sharks, Glyphis garricki and Glyphis glyphis. These represent the first records of both species in PNG since the 1960s and 1970s and highlight the lack of studies of shark biodiversity in PNG. Two individuals of G. garricki and three individuals of G. glyphis were recorded from coastal marine waters of the Daru region of PNG in October and November 2014. The two G. garricki specimens were small individuals estimated to be 100–105 cm and ~113 cm total length (TL). The three G. glyphis specimens were all mature, one a pregnant female and two adult males. These are the first adults of G. glyphis recorded to date providing a more accurate maximum size for this species, i.e. ~260 cm TL. A single pup which was released from the pregnant female G. glyphis, was estimated to be ~65 cm TL. Anecdotal information from the fishers of pregnant females of G. glyphis containing 6 or 7 pups provides the first estimate of litter size for this species. The jaws of the pregnant female G. glyphis were retained and a detailed description of the dentition is provided, since adult dentition has not been previously documented for this species. Genetic analyses confirmed the two species cluster well within samples from these species collected in northern Australia

Tightening of tropical ascent and high clouds key to precipitation change in a warmer climate

The change of global-mean precipitation under global warming and interannual variability is predominantly controlled by the change of atmospheric longwave radiative cooling. Here we show that tightening of the ascending branch of the Hadley Circulation coupled with a decrease in tropical high cloud fraction is key in modulating precipitation response to surface warming. The magnitude of high cloud shrinkage is a primary contributor to the intermodel spread in the changes of tropical-mean outgoing longwave radiation (OLR) and global-mean precipitation per unit surface warming (dP/dTs) for both interannual variability and global warming. Compared to observations, most Coupled Model Inter-comparison Project Phase 5 models underestimate the rates of interannual tropical-mean dOLR/dTs and global-mean dP/dTs, consistent with the muted tropical high cloud shrinkage. We find that the five models that agree with the observation-based interannual dP/dTs all predict dP/dTs under global warming higher than the ensemble mean dP/dTs from the ∼20 models analysed in this study

Epithelial immunomodulation by aerosolized Toll-like receptor agonists prevents allergic inflammation in airway mucosa in mice

Allergic asthma is a chronic inflammatory respiratory disease associated with eosinophilic infiltration, increased mucus production, airway hyperresponsiveness, and airway remodeling. Epidemiologic data reveal that the prevalence of allergic sensitization and associated diseases has increased in the twentieth century. This has been hypothesized to be partly due to reduced contact with microbial organisms (the hygiene hypothesis) in industrialized society. Airway epithelial cells, once considered a static physical barrier between the body and the external world, are now widely recognized as immunologically active cells that can initiate, maintain, and restrain inflammatory responses, such as those that mediate allergic disease. Airway epithelial cells can sense allergens via expression of myriad Toll-like receptors (TLRs) and other pattern-recognition receptors. We sought to determine whether the innate immune response stimulated by a combination of Pam2CSK4 (“Pam2”, TLR2/6 ligand) and a class C oligodeoxynucleotide ODN362 (“ODN”, TLR9 ligand), when delivered together by aerosol (“Pam2ODN”), can modulate the allergic immune response to allergens. Treatment with Pam2ODN 7 days before sensitization to House Dust Mite (HDM) extract resulted in a strong reduction in eosinophilic and lymphocytic inflammation. This Pam2ODN immunomodulatory effect was also seen using Ovalbumin (OVA) and A. oryzae (Ao) mouse models. The immunomodulatory effect was observed as much as 30 days before sensitization to HDM, but ineffective just 2 days after sensitization, suggesting that Pam2ODN immunomodulation lowers the allergic responsiveness of the lung, and reduces the likelihood of inappropriate sensitization to aeroallergens. Furthermore, Pam2 and ODN cooperated synergistically suggesting that this treatment is superior to any single agonist in the setting of allergen immunotherapy

FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy.

Gene copy number alterations, tumor cell stemness, and the development of platinum chemotherapy resistance contribute to high-grade serous ovarian cancer (HGSOC) recurrence. Stem phenotypes involving Wnt-β-catenin, aldehyde dehydrogenase activities, intrinsic platinum resistance, and tumorsphere formation are here associated with spontaneous gains in Kras, Myc and FAK (KMF) genes in a new aggressive murine model of ovarian cancer. Adhesion-independent FAK signaling sustained KMF and human tumorsphere proliferation as well as resistance to cisplatin cytotoxicity. Platinum-resistant tumorspheres can acquire a dependence on FAK for growth. Accordingly, increased FAK tyrosine phosphorylation was observed within HGSOC patient tumors surviving neo-adjuvant chemotherapy. Combining a FAK inhibitor with platinum overcame chemoresistance and triggered cell apoptosis. FAK transcriptomic analyses across knockout and reconstituted cells identified 135 targets, elevated in HGSOC, that were regulated by FAK activity and β-catenin including Myc, pluripotency and DNA repair genes. These studies reveal an oncogenic FAK signaling role supporting chemoresistance

Quantum computation with two-level trapped cold ions beyond Lamb-Dicke limit

We propose a simple scheme for implementing quantum logic gates with a string of two-level trapped cold ions outside the Lamb-Dicke limit. Two internal states of each ion are used as one computational qubit (CQ) and the collective vibration of ions acts as the information bus, i.e., bus qubit (BQ). Using the quantum dynamics for the laser-ion interaction as described by a generalized Jaynes-Cummings model, we show that quantum entanglement between any one CQ and the BQ can be coherently manipulated by applying classical laser beams. As a result, universal quantum gates, i.e. the one-qubit rotation and two-qubit controlled gates, can be implemented exactly. The required experimental parameters for the implementation, including the Lamb-Dicke (LD) parameter and the durations of the applied laser pulses, are derived. Neither the LD approximation for the laser-ion interaction nor the auxiliary atomic level is needed in the present scheme.Comment: 12 pages, no figures, to appear in Phys. Rev.

Kinase inhibitor pulldown assay identifies a chemotherapy response signature in triple-negative breast cancer based on purine-binding proteins

UNLABELLED: Triple-negative breast cancer (TNBC) constitutes 10%-15% of all breast tumors. The current standard of care is multiagent chemotherapy, which is effective in only a subset of patients. The original objective of this study was to deploy a mass spectrometry (MS)-based kinase inhibitor pulldown assay (KIPA) to identify kinases elevated in non-pCR (pathologic complete response) cases for therapeutic targeting. Frozen optimal cutting temperature compound-embedded core needle biopsies were obtained from 43 patients with TNBC before docetaxel- and carboplatin-based neoadjuvant chemotherapy. KIPA was applied to the native tumor lysates that were extracted from samples with high tumor content. Seven percent of all identified proteins were kinases, and none were significantly associated with lack of pCR. However, among a large population of off-target purine-binding proteins (PBP) identified, seven were enriched in pCR-associated samples ( SIGNIFICANCE: The identification of pretreatment predictive biomarkers for pCR in response to neoadjuvant chemotherapy would advance precision treatment for TNBC. To complement standard proteogenomic discovery profiling, a KIPA was deployed and unexpectedly identified a seven-member non-kinase PBP pCR-associated signature. Individual members served diverse pathways including IFN gamma response, nuclear import of DNA repair proteins, and cell death

Copy number alterations associated with clinical features in an underrepresented population with breast cancer

As the most incident tumor among women worldwide, breast cancer is a heterogeneous disease. Tremendous efforts have been made to understand how tumor characteristics as histological type, molecular subtype, and tumor microenvironment collectively influence disease diagnosis to treatment, which impact outcomes. Differences between populations and environmental and cultural factors have impacts on the origin and evolution of the disease, as well as the therapeutic challenges that arise due to these factors. We, then, compared copy number variations (CNVs) in mucinous and nonmucinous luminal breast tumors from a Brazilian cohort to investigate major CNV imbalances in mucinous tumors versus non‐mucinous luminal tumors, taking into account their clinical and pathological features.48 breast tumor samples and 48 matched control blood samples from Brazilian women were assessed for CNVs by chromosome microarray. Logistic regression and random forest models were used in order to assess CNVs in chromosomal regions from tumors.CNVs that were identified in chromosomes 1, 5, 8, 17, 19, and 21 classify tumors according to their histological type, ethnicity, disease stage, and familial history.Copy number alterations described in this study provide a better understanding of the landscape of genomic aberrations in mucinous breast cancers that are associated with clinical features.77FAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo2013/25683-3; 2015/18830-

Phase 2 Study of Neoadjuvant Enzalutamide and Paclitaxel for Luminal Androgen Receptor-Enriched TNBC: Trial Results and Insights Into “ARness”

Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m2 weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a pathologic complete response or residual cancer burden-I. ZT was safe, with no unexpected side effects. An iAR of at least 70% had a positive predictive value of 0.92 and a negative predictive value of 0.97 in predicting LAR-enriched TNBC according to RNA-based assays. Our data support future trials of AR blockade in early-stage LAR-enriched TNBC