91 research outputs found

    The pitfalls of deciding whether a quantum channel is (conjugate) degradable and how to avoid them

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    To decide whether a quantum channel is degradable is relatively easy: one has to find at least one example of a degrading quantum channel. But in general, no conclusive criterion exists to show the opposite. Using elementary methods we derive a necessary and sufficient condition to decide under what circumstances the conclusion is unambiguous. The findings lead to an extension of the antidegradability region for qubit and qutrit transpose depolarizing channels. In the qubit case we reproduce the known results for the class of qubit depolarizing channels (due to their equivalence). One of the consequences is that the optimal qubit and qutrit asymmetric cloners possess a single-letter quantum capacity formula. We also investigate the ramifications of the criterion for the search of exclusively conjugate degradable channels.Comment: v2: Full rank assumption added to the main theorem; to appear in Open Systems & Information Dynamic

    Symmetric Extendability of Quantum States and the Extreme Limits of Quantum Key Distribution

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    We investigate QKD protocols with two-way classical post-processing that are based on the well-known six-state and BB84 signal states. In these QKD protocols, the source (Alice) sends quantum signals to the receiver (Bob), who measures them, leaving only classical data on both sides. Our goal is to find the highest value of the quantum bit-error rate (QBER) QQ for which two-way classical post-processing protocols on the data can distill secret keys. Using the BB84 signal states, such protocols currently exist for Q<15Q<\frac{1}{5}. On the other hand, for Q14Q\geq\frac{1}{4} no such protocol can exist as the observed data is compatible with an intercept-resend attack. This leaves the interesting question of whether successful two-way protocols exist in the interval 15Q<14\frac{1}{5}\leq Q<\frac{1}{4}. For the six-state signal states, the corresponding interval is known to be 5510Q<13\frac{5-\sqrt{5}}{10}\leq Q<\frac{1}{3}. We search for two-way protocols because it turns out that within these intervals Alice and Bob's correlations are symmetrically extendable, meaning that Bob and the eavesdropper (Eve) are completely indistinguishable from Alice's point of view, making any one-way Alice-to-Bob post-processing protocol insecure. A two-way protocol might be able to break the symmetry between Bob and Eve, and it must do so in order to distill a secret key because any two-way protocol will necessarily terminate with a one-way communication step, at which point the symmetric extendability of Alice and Bob's updated correlations must be checked again. We first show that the search for two-way protocols breaking the symmetric extendability of Alice and Bob's correlations can be restricted to a search over post-selection protocols if all we care about is whether secret key can at all be distilled and not about the rate of distillation. We then provide strong analytical and numerical evidence to suggest that no two-way classical post-processing protocol exists within the gap when the six-state signal states are used. Under quantum entanglement distillation protocols, it is known that secret key can be distilled right up to the intercept-resend bounds of 14\frac{1}{4} and 13\frac{1}{3} for the BB84 and six-state signal states, respectively. We therefore want to know whether classical post-processing protocols are just as good at distilling secret keys as quantum ones. Our results appear to indicate that they are not

    量子写像における正値性と完全正値性の差異

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    学位の種別: 課程博士審査委員会委員 : (主査)東京大学准教授 筒井 泉, 国立情報学研究所准教授 蓮尾 一郎, 東京大学教授 緒方 芳子, 東京大学准教授 藤堂 真治, 東京大学教授 勝本 信吾University of Tokyo(東京大学

    Diverse Applications of Nanomedicine

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    The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic. \ua9 2017 American Chemical Society

    Urinary Stents

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    This open access book provides a concise overview of a range of aspects related to urinary stents. Sections within the work cover clinical and recent technological advancements in the field. Chapters feature detailed coverage of the different surgical, pharmacological and palliative treatments currently available. Insight is also given on current limitations of urinary stents and how these can be overcome by utilizing anti-biofilm coatings; new biomaterials, drug-eluting stents, and biodegradable stents. Therefore, enabling the reader to systematically gain a detailed understanding of the subject. Urinary Stents is a practical, multi-disciplinary focused resource on the complications and applications of ureteral, urethral and prostatic stents in day-to-day clinical practice. A vital read for all medical professionals and researchers who work in this area

    Nanoparticles: Potential for Use to Prevent Infections

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    One of the major issues related to medical devices and especially urinary stents are infections caused by different strains of bacteria and fungi, mainly in light of the recent rise in microbial resistance to existing antibiotics. Lately, it has been shown that nanomaterials could be superior alternatives to conventional antibiotics. Generally, nanoparticles are used for many applications in the biomedical field primarily due to the ability to adjust and control their physicochemical properties as well as their great reactivity due to the large surface-to-volume ratio. This has led to the formation of a new research field called nanomedicine which can be defined as the use of nanotechnology and nanomaterials in diagnostics, imaging, observing, prevention, control, and treatment of diseases. For example, coverings or coatings based on nanomaterials are now seen as a promising strategy for preventing or treating biofilms formation on healthcare kits, implants, and medical devices. Toxicity, inappropriate delivery, or degradation of conventionally used drugs for the treatment of infections may be avoided by using nanoparticles without or with encapsulated/immobilized active substances. Most of the materials which are used and examined for the preparation of the nanoparticles with encapsulated/immobilized active substances or smart reactive nanomaterials with antimicrobial effects are polymers, naturally derived antimicrobials, metal-based and non-metallic materials. This chapter provides an overview of the current state and future perspectives of the nanoparticle-based systems based on these materials for prevention, control, or elimination of biofilm-related infections on urinary stents. It also addresses manufacturing conditions indicating the huge potential for the improvement of existing and development of new promising stent solutions

    Urinary Stents

    Get PDF
    This open access book provides a concise overview of a range of aspects related to urinary stents. Sections within the work cover clinical and recent technological advancements in the field. Chapters feature detailed coverage of the different surgical, pharmacological and palliative treatments currently available. Insight is also given on current limitations of urinary stents and how these can be overcome by utilizing anti-biofilm coatings; new biomaterials, drug-eluting stents, and biodegradable stents. Therefore, enabling the reader to systematically gain a detailed understanding of the subject. Urinary Stents is a practical, multi-disciplinary focused resource on the complications and applications of ureteral, urethral and prostatic stents in day-to-day clinical practice. A vital read for all medical professionals and researchers who work in this area

    Multiplexed angiogenic biomarker quantification on single cells

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    Clinical and biomedical research seeks single-cell quantification to better understand their roles in a complex, multi-cell environment. Recently, quantification of vascular endothelial growth factor receptors (VEGFRs) provided important insights into endothelial cell (EC) characteristics and response in tumor microenvironments. However, data on other angiogenic receptors, such as platelet derived growth factor receptors (PDGFRs), Tie receptors, are also necessary for the development of an accurate angiogenesis model. To gain insights on the involvement of these angiogenic receptors in angiogenesis, I develop a method to quantify receptor concentrations as well as the cell-by-cell heterogeneity. I establish protocols to measure cell membrane VEGFR, NRP1, Tie2, and PDGFR concentration on several cell and tissue models including human dermal fibroblasts (HDFs) in vitro, a 2D endothelial/fibroblast co-culture model in vitro, and a patient-derived xenograft (PDX) model of glioblastoma (GBM). I demonstrate VEGF-A165-mediated downregulation of membrane PDGFRα (~25%) and PDGFRβ (~30%) on HDFs, following a 24-hour treatment. This supports the idea that VEGF-A165 acts independently of VEGFRs to signal through PDGFRα and PDGFRβ. I uncover high intratumoral heterogeneity within the GBM PDX model, with tumor EC-like subpopulations having high concentrations of membrane VEGFR1, VEGFR2, EGFR, IGFR, and PDGFRs. To gain greater insights into cell heterogeneity and examine angiogenic signaling pathways as a whole, I utilize the unique spectral properties of quantum dots (Qdots), and combines Qdots with qFlow cytometry, to dually quantify VEGFR1 and VEGFR2 on human umbilical vein endothelial cells (HUVECs). To enable this quantification, I reduce nonspecific binding between Qdot-conjugated antibodies and cells, identify optimal labeling conditions, and establish that 800 – 20,000 is the dynamic range where accurate Qdot-enabled quantification can be achieved. Through these optimizations we demonstrate measurement of 1,100 VEGFR1 and 6,900 VEGFR2 per HUVEC. 24 h VEGF-A165 treatment induce ~90% upregulation of VEGFR1 and ~30% downregulation of VEGFR2 concentration. We further analyze HUVEC heterogeneity and observe that 24 h VEGF-A165 treatment induces ~15% decrease in VEGFR2 heterogeneity. Overall, we demonstrate experimental and analysis strategies for quantifying two or more RTKs at single-level using Qdots, which will provide new insights into biological systems

    Multivalent nanoparticles for the treatment of ocular diseases

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    The present work investigated the multivalent binding of nanoparticles towards cells and how they can be utilized for treating severe ocular diseases. It was more than 100 years ago when Paul Ehrlich coined the idea of the ‘Magic Bullet’, a personalized and tailored drug that precisely targets diseased cells in the human body and leaves healthy cells untouched. Among many examples that resemble this concept, targeted delivery of nanoparticles to specific tissues is often designated as the most promising one. Active targeting, which is addressing nanoparticles to individual tissues, is usually achieved by conjugating ligand molecules to the colloidal surface. Moreover, since multiple ligand molecules can be attached to the particle corona, highly sophisticated multivalent material-cell interactions are imaginable. Although they add another layer of complexity to the system, they may ultimately determine a particle’s fate. A prominent example in which nanoparticle formulations have gained much interest recently is the treatment of pathologic neovascularizations in the posterior eye segment. Their outstanding features, which include the encapsulation of drugs, the accumulation in areas of increased vascular permeability or the controlled release of active ingredients, has prompted immense research efforts for the intravitreal but also systemic application. In addition, certain nanomaterials exhibit unique anti-proliferative and anti-oxidative effects that could impressively expand and improve the current therapeutic arsenal (Chapter 1). However, although there are tremendous efforts going into the design and development of nanoparticle formulations, the actual amount of novel formulations entering clinical trials or being approved is very limited. A potential pitfall that could reduce nanoparticle applicability is the loss of nanoparticle targeting efficacy due to ligand affinity decrease, which can be a consequence of ligand attachment to the nanoparticle polymer corona. EXP3174, a non-peptide angiotensin receptor blocker, underwent a 580-fold decreased receptor binding affinity after conjugation to a PEG chain. When multivalently presented on a nanoparticle surface, initially lost affinity was rapidly regained, which was a consequence of the nanoparticle’s capability to bind several receptors simultaneously (Chapter 3). However, for this to happen, a sufficiently high receptor density is required. Owing to the weak affinity of a monovalent nanoparticle-cell interaction compared to the multivalent interaction, the colloids gained the ability to differently target cells depending on their receptor expression levels. For this reason, EXP3174-targeted Qdots strongly associated with NCI-295R cells that showed a high AT1R expression, but not with HeLa cells with a low receptor expression. The receptor’s physiological ligand angiotensin II is a potent growth factor and of critical importance for neovascularizations in the posterior eye segment. Hence, the type-1 receptor in the ocular vasculature is a logical target for nanoparticles that are capable of blocking the receptor over an extended period of time. EXP3174-Qdots specifically accumulated in the retinal and choroidal vessels but not in off-target tissue such as the kidney, which was attributed to the multivalent ligand display. Remarkably, the nanoparticle’s blood circulation time did not suffer from ligand attachment but, in contrast, was improved (Chapter 4). Since the semiconductor Qdots were mainly used as reporter particles in the preceding studies due to their outstanding fluorescence properties, the multivalent binding and blocking of AT1 receptors was transferred to drug-polymer-conjugates as potential therapeutic agents. EXP3174-modified multi-arm PEGs and generation 5 PAMAM dendrimers both blocked AT1R receptors with nanomolar affinity. Due to their unique microarchitecture PAMAM dendrimers retained a 6 fold higher receptor binding affinity than the branched PEGs, whose lowered affinity was presumably due to hydrophobic interactions between EXP3174 and the polymer. Both conjugates showed no measurable in vitro cytotoxicity, which was impressively in stark contrast to the unmodified PAMAM dendrimers (Chapter 5). Compared with antagonist-modified nanoparticles which are not immediately taken up but rest at the cell membrane, agonist-modified colloids are promptly endocytosed into the cell after receptor activation. However, as tested with calcium mobilization experiments the instant cell uptake did not impede the formation of multivalent nanoparticle-cell interactions for angiotensin II-targeted Qdots, as the agonist-targeted colloids exhibited a 30-fold higher affinity than the free ligand. In a cell binding model the ligand-modified Qdots exclusively interacted with receptor expressing cells. The resulting receptor-mediated endocytosis occurred via clathrin-coated pits and was inhibitable with receptor antagonists. Interestingly, although the immediate uptake did not suppress multivalent binding formation, the multivalency was lower than observed for antagonist-modified nanoparticles (Chapter 6). The trabecular meshwork, a sponge-like tissue in the iridocorneal angle of the eye is responsible for aqueous humor drainage and thus pivotal key player in the pathogenesis of primary open-angle glaucoma. Nanoparticles coated with cyclic RGD peptides and targeted towards integrin receptors were rapidly and massively endocytosed into human trabecular meshwork cells. The association to the cultured trabecular meshwork cells was significantly higher than the association to the prominent αvβ3 integrin-overexpressing glioblastoma cell line U87-MG. As demonstrated by real-time PCR and western blotting, the cyclic RGD peptide mitigated connective tissue growth factor-induced fibrotic events such as matrix deposition and stress fiber formation. The experimental data convincingly illustrated why cyclic RGD peptides are powerful targeting moieties when the aim is to address nanoparticles, e.g. for gene delivery, specifically to the trabecular meshwork (Chapter 7). The present work unveiled the immense potential of multivalent nanoparticle-cell interactions and promising applications thereof. Not only can nanoparticle multivalency be utilized to differentially target organs, tissue and cells based on divergent receptor expression levels, but it can also be used to amplify cell-specific targeting. The difference in multivalent behavior between antagonistic and agonistic nanoparticles targeting the AT1 receptor was clearly evident and a result of different receptor responses upon ligand binding. In this regard, especially the binding of antagonistic nanoparticles to angiotensin receptors of retinal and choroidal blood vessels and thus blockade of these receptors holds great potential for tissue-specific attenuation of pathologic neovascularizations. In a similar fashion, blockade of integrin receptors by cyclo(RGDfC)-coated nanoparticles and cell-specific delivery of therapeutic agents to the trabecular meshwork is a promising strategy to enhance glaucoma treatment options that currently appear on the horizon. Taken together, the newly gained understanding of nanoparticles and their multivalent interactions with cells has significant potential to carve out new paths for treating severe diseases of the anterior and posterior eye segment
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