Observation of time correlation function of multimode two-photon pairs on a rubidium D2_2 line

We report the generation of a type-I multimode two-photon state on a rubidium D$_2$ line (780 nm) using periodically poled KTiOPO$_4$ crystals. With a degenerate optical parametric oscillator far below threshold, we observe an oscillatory correlation function, the cross-correlation between two photons shows a cavity bandwidth of about 7.8 MHz. We also use a Fabry-P$\acute{\rm{e}}$rot etalon to filter its most longitudinal modes and observe its time correlation function. The experimental data are well fitted to theoretical curves. This system could be utilized for demonstrating storage and retrieval of narrowband photons in Rb atomic ensembles, which is important for long-distance quantum communication.Comment: 4 pages, 3 figures, submitted for publication on 29 April 200

Scientific and Regulatory Perspective on Monoclonal Antibody Biosimilars

Similar biotherapeutic products (SBPs), also called biosimilars, exhibit similar biological and clinical properties to authorized reference products. Biosimilars, including small molecules like erythropoietin and complex macromolecules like monoclonal antibodies (mAbs), have been used extensively in disease treatment. Monoclonal antibody biosimilars have gradually become a dominant development in the global pharmaceutical industry since their patents or data protection have been expired or nearing expiration. Since the mAb biosimilars are complex biological macromolecules with various post-translation modifications, it is important to evaluate whether these tiny differences significantly affect the quality. From a regulatory perspective, the comparability study needs to be performed to demonstrate that the quality, safety, and efficacy are similar to the biological reference. Based on these comprehensive comparative results, the indicated extrapolation might be acceptable. Post-market surveillance is also required because of unexpected biological variation caused by slightly different manufacturing processes. This chapter presents the scientific and regulatory considerations for monoclonal antibody biosimilar products for manufactures and for the regulatory authorities to administrate wisely and comprehensively

The Hot and Clumpy Molecular Cocoon Surrounding the Ultracompact HII Region G5.89-0.39

We present observations of CH3CN (12-11) emission at a resolution of 2" toward the shell-like ultracompact HII region G5.89-0.39 with the Submillimeter Array. The integrated CH3CN emission reveals dense and hot molecular cocoon in the periphery of the HII region G5.89-0.39, with a CH3CN deficient region roughly centered at G5.89-0.39. By analyzing the CH3CN emission using population diagram analysis, we find, for the first time, a decreasing temperature structure from 150 to 40 K with the projected distance from Feldt's star, which is thought to be responsible for powering the HII region. Our results further indicate that the majority of the heating energy in the observed dense gas is supplied by the Feldt's star. From the derived CH3CN column density profile, we conclude that the dense gas is not uniformly-distributed but centrally-concentrated, with a power-law exponent of 5.5 for r < 8000 AU, and 2.0 for 8000 AU < r < 20000 AU, where r is the distance to Feldt's star. The estimated large power index of 5.5 can be attributed to an enhancement of CH3CN abundance in the close vicinity of Feldt's star.Comment: accepted for publication in The Astrophysical Journal Letter

Lipid-Based Antimicrobial Delivery-Systems for the Treatment of Bacterial Infections

Many nanotechnology-based antimicrobials and antimicrobial-delivery-systems have been developed over the past decades with the aim to provide alternatives to antibiotic treatment of infectious-biofilms across the human body. Antimicrobials can be loaded into nanocarriers to protect them against de-activation, and to reduce their toxicity and potential, harmful side-effects. Moreover, antimicrobial nanocarriers such as micelles, can be equipped with stealth and pH-responsive features that allow self-targeting and accumulation in infectious-biofilms at high concentrations. Micellar and liposomal nanocarriers differ in hydrophilicity of their outer-surface and inner-core. Micelles are self-assembled, spherical core-shell structures composed of single layers of surfactants, with hydrophilic head-groups and hydrophobic tail-groups pointing to the micellar core. Liposomes are composed of lipids, self-assembled into bilayers. The hydrophilic head of the lipids determines the surface properties of liposomes, while the hydrophobic tail, internal to the bilayer, determines the fluidity of liposomal-membranes. Therefore, whereas micelles can only be loaded with hydrophobic antimicrobials, hydrophilic antimicrobials can be encapsulated in the hydrophilic, aqueous core of liposomes and hydrophobic or amphiphilic antimicrobials can be inserted in the phospholipid bilayer. Nanotechnology-derived liposomes can be prepared with diameter

Liposomes with Water as a pH-Responsive Functionality for Targeting of Acidic Tumor and Infection Sites

A lipid named DCPA was synthesized under microwave-assisted heating. DCPA possesses a pyridine betaine, hydrophilic group that can be complexed with water through hydrogen bonding (DCPA-H2O). DCPA-H2O liposomes became protonated relatively fast already at p

FOXO/Fringe is necessary for maintenance of the germline stem cell niche in response to insulin insufficiency

AbstractThe stem cell niche houses and regulates stem cells by providing both physical contact and local factors that regulate stem cell identity. The stem cell niche also plays a role in integrating niche-local and systemic signals, thereby ensuring that the balance of stem cells meets the needs of the organism. However, it is not clear how these signals are merged within the niche. Nutrient-sensing insulin/FOXO signaling has been previously shown to directly control Notch activation in the Drosophila female germline stem cell (GSC) niche, which maintains the niche and GSC identity. Here, we demonstrate that FOXO directly activates transcription of fringe, a gene encoding a glycosyltransferase that modulates Notch glycosylation. Fringe facilitates Notch inactivation in the GSC niche when insulin signaling is low. We also show that the Notch ligand predominantly involved is GSC niche-derived Delta. These results reveal that FOXO-mediated regulation of fringe links the insulin and Notch signaling pathways in the GSC niche in response to nutrition, and emphasize that stem cells are regulated by complex interactions between niche-local and systemic signals

Distributed Representations of Signed Networks

Recent successes in word embedding and document embedding have motivated researchers to explore similar representations for networks and to use such representations for tasks such as edge prediction, node label prediction, and community detection. Such network embedding methods are largely focused on finding distributed representations for unsigned networks and are unable to discover embeddings that respect polarities inherent in edges. We propose SIGNet, a fast scalable embedding method suitable for signed networks. Our proposed objective function aims to carefully model the social structure implicit in signed networks by reinforcing the principles of social balance theory. Our method builds upon the traditional word2vec family of embedding approaches and adds a new targeted node sampling strategy to maintain structural balance in higher-order neighborhoods. We demonstrate the superiority of SIGNet over state-of-the-art methods proposed for both signed and unsigned networks on several real world datasets from different domains. In particular, SIGNet offers an approach to generate a richer vocabulary of features of signed networks to support representation and reasoning.Comment: Published in PAKDD 201

Proton-mediated burst of dual-drug loaded liposomes for biofilm dispersal and bacterial killing

Exposure of infectious biofilms to dispersants induces high bacterial concentrations in blood that may cause sepsis. Preventing sepsis requires simultaneous biofilm dispersal and bacterial killing. Here, self-targeting DCPA(2-(4-((1,5-bis(octadecenoyl)1,5-dioxopentan-2-yl)carbamoyl)pyridin-1-ium-1-yl)acetate) liposomes with complexed water were self-assembled with ciprofloxacin loaded in-membrane and PEGylated as a lipid-membrane component, together with bromelain loaded in-core. Inside biofilms, DCPA-H2O and PEGylated ciprofloxacin became protonated, disturbing the balance in the lipid-membrane to cause liposome-burst and simultaneous release of bromelain and ciprofloxacin. Simultaneous release of bromelain and ciprofloxacin enhanced bacterial killing in Staphylococcus aureus biofilms as compared with free bromelain and/or ciprofloxacin. After tail-vein injection in mice, liposomes accumulated inside intra-abdominal staphylococcal biofilms. Subsequent liposome-burst and simultaneous release of bromelain and ciprofloxacin yielded degradation of the biofilm matrix by bromelain and higher bacterial killing without inducing septic symptoms as obtained by injection of free bromelain and ciprofloxacin. This shows the advantage of simultaneous release from liposomes of bromelain and ciprofloxacin inside a biofilm