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Some cancer cells rely heavily on non-essential biomolecules for survival, growth, and proliferation. Enzyme based therapeutics can eliminate these biomolecules, thus specifically targeting neoplastic cells; however, enzyme therapeutics are susceptible to immune clearance, exhibit short half-lives, and require frequent administration. Encapsulation of therapeutic cargo within biocompatible and biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) is a strategy for controlled release. Unfortunately, PLGA NPs exhibit burst release of cargo shortly after delivery or upon introduction to aqueous environments where they decompose via hydrolysis. Here, we show the generation of hybrid silica-coated PLGA (SiLGA) NPs as viable drug delivery vehicles exhibiting sub-200 nm diameters, a metastable Zeta potential, and high loading efficiency and content. Compared to uncoated PLGA NPs, SiLGA NPs offer greater retention of enzymatic activity and slow the burst release of cargo. Thus, SiLGA encapsulation of therapeutic enzymes, such as asparaginase, could reduce frequency of administration, increase half-life, and improve efficacy for patients with a range of diseases.

Circularizable oligonucleotide probes can detect short DNA sequences with single-base resolution at the site of ligation and can be amplified by rolling circle amplification (RCA) using strand displacing polymerases. A secondary amplification scheme was developed that uses the loop-mediated amplification reaction concurrent with RCA to achieve rapid signal development from the starting circular molecules. This isothermal reaction was found to be significantly faster than the comparable hyperbranching amplification method and could detect 100 circular copies in less than 1 h.

Circulating tumor cells (CTCs) are exfoliated at various stages of cancer, and could provide invaluable information for the diagnosis and prognosis of cancers. There is an urgent need for the development of cost-efficient and scalable technologies for rare CTC enrichment from blood. Here we report a novel method for isolation of rare tumor cells from excess of blood cells using gas-filled buoyant immuno-microbubbles (MBs). MBs were prepared by emulsification of perfluorocarbon gas in phospholipids and decorated with anti-epithelial cell adhesion molecule (EpCAM) antibody. EpCAM-targeted MBs efficiently (85%) and rapidly (within 15 minutes) bound to various epithelial tumor cells suspended in cell medium. EpCAM-targeted MBs efficiently (88%) isolated frequent tumor cells that were spiked at 100,000 cells/ml into plasma-depleted blood. Anti-EpCAM MBs efficiently (>77%) isolated rare mouse breast 4T1, human prostate PC-3 and pancreatic cancer BxPC-3 cells spiked into 1, 3 and 7 ml (respectively) of plasma-depleted blood. Using EpCAM targeted MBs CTCs from metastatic cancer patients were isolated, suggesting that this technique could be developed into a valuable clinical tool for isolation, enumeration and analysis of rare cells.

La présente étude correspond à une approche pluridisciplinaire menée en étroite collaboration entre des géologues, des chimistes et des industriels de la céramique. Les résultats confirment l’étroite relation existante entre la composition des argiles et la qualité du produit céramique final. Les briquettes obtenues, dans les mêmes conditions, à partir de deux argiles marocaines assez différentes du point de vue chimique et minéralogique, présentent des caractéristiques technologiques bien distinctes. l’utilisation d’adjuvants minéraux, bien sélectionnés, contribue à l’équilibrage des argiles brutes et conduit à une nette amélioration de la qualité du produit céramique, notamment une réduction de leur retrait à la cuisson et une augmentation de leur résistance à la flexion. Concernant l’effet du processus de fabrication, l’application de l’engobe et de l’émail, s’avère être à l’origine de bombement des carreaux lors de la cuisson, en raison vraisemblablement de la différence des coefficients de dilatation des deux milieux argile et émail. This study is conducted in a multidisciplinary collaboration between geologists, chemists and industrial ceramics. The results confirm the close ralatioship existing between the composition of clays and quality of the finished ceramic pieces. The obtained specimens, under the same conditions, from two moroccan clays that are different on the chimico-mineralogical point of view, present distinct technological characteristics. The use of well selected mineral adjuvants, contributes to the balancing of raw clays and leads to a marked improvement in the quality of the ceramic product, including a reduction on their firing shrinkage and an increase of flexural strength. Concerning the effect of the manufacturing process, the application of the glaze, turns out to be the cause of bulging tiles during firing, probably because of the difference in thermal expansion coefficients of two materials clay and glaze.

High affinity and specificity are considered essential for affinity reagents and molecularly-targeted therapeutics, such as monoclonal antibodies. However, life's own molecular and cellular machinery consists of lower affinity, highly multivalent interactions that are metastable, but easily reversible or displaceable. With this inspiration, we have developed a DNA-based reagent platform that uses massive avidity to achieve stable, but reversible specific recognition of polyvalent targets. We have previously selected these DNA reagents, termed DeNAno, against various cells and now we demonstrate that DeNAno specific for protein targets can also be selected. DeNAno were selected against streptavidin-, rituximab- and bevacizumab-coated beads. Binding was stable for weeks and unaffected by the presence of soluble target proteins, yet readily competed by natural or synthetic ligands of the target proteins. Thus DeNAno particles are a novel biomolecular recognition agent whose orthogonal use of avidity over affinity results in uniquely stable yet reversible binding interactions.

Circulating tumor cells (CTCs) are exfoliated at various stages of cancer, and could provide invaluable information for the diagnosis and prognosis of cancers. There is an urgent need for the development of cost-efficient and scalable technologies for rare CTC enrichment from blood. Here we report a novel method for isolation of rare tumor cells from excess of blood cells using gas-filled buoyant immuno-microbubbles (MBs). MBs were prepared by emulsification of perfluorocarbon gas in phospholipids and decorated with anti-epithelial cell adhesion molecule (EpCAM) antibody. EpCAM-targeted MBs efficiently (85%) and rapidly (within 15 minutes) bound to various epithelial tumor cells suspended in cell medium. EpCAM-targeted MBs efficiently (88%) isolated frequent tumor cells that were spiked at 100,000 cells/ml into plasma-depleted blood. Anti-EpCAM MBs efficiently (>77%) isolated rare mouse breast 4T1, human prostate PC-3 and pancreatic cancer BxPC-3 cells spiked into 1, 3 and 7 ml (respectively) of plasma-depleted blood. Using EpCAM targeted MBs CTCs from metastatic cancer patients were isolated, suggesting that this technique could be developed into a valuable clinical tool for isolation, enumeration and analysis of rare cells.

Sperm motility is an important concept in fertility research. To this end, single spot laser tweezers have been used to quantitatively analyze the motility of individual sperm. However, this method is limited with throughput (single sperm per spot), lacks the ability of in-situ sorting based on motility and chemotaxis, requires high laser power (hundreds of milliWatts) and can not be used to dynamically monitor changes in sperm swimming behavior under the influence of a laser beam. Here, we report a continuous 3-D ring-shaped laser trap which could be used for multi-level and high-throughput (tens to hundred sperm per ring) sperm sorting based on their motility and chemotaxis. Under a laser power of only tens of milliWatts, human sperm with low to medium velocity are slowed down, stopped, or forced to change their trajectories to swim along the ring due to the optical gradient force in the radial direction. This is the first demonstration of parallel sperm sorting based on motility with optical trapping technology. In addition, by making the sperm swimming along the circumference of the ring, the effect of laser radiation, optical force and external obstacles on sperm energetics are investigated in a more gentle and quantitative way. The application of this method could be extended to motility and bio-tropism studies of other self-propelled cells, such as algae and bacteria.

A three-dimensional (3D) ring-shaped laser trap has been built using axicons. The diameter of this laser trap ranges from 70 to 140 mum and is adjusted by simply changing the position of one axicon in the optical path. Parallel 3D trapping of 5 mum silica microspheres and 3D confinement of cells along the ring are demonstrated. In this system the special optical properties of axicons are used to create a continuous annular trap with high power efficiency and a constant numerical aperture. This new approach, without any mechanical scanning, offers significant potential for applications in cell motility analysis and biotropism studies.

To study the chemotactic response of sperm to an egg and to characterize sperm motility, an annular laser trap based on axicons is designed, simulated with the ray-tracing tool, and implemented. The diameter of the trapping ring can be adjusted dynamically for a range of over 400 microm by simply translating one axicon along the optical axis. Trapping experiments with microspheres and dog sperm demonstrate the feasibility of the system, and the power requirement agrees with theoretical expectation. This new type of laser trapping could provide a prototype of a parallel, objective, and quantitative tool for animal fertility and biotropism study.

As a powerful and noninvasive tool, laser trapping has been widely applied for the confinement and physiological study of biological cells and organelles. Researchers have used the single spot laser trap to hold individual sperm and quantitatively evaluated the motile force generated by a sperm. Early studies revealed the relationship between sperm motility and swimming behavior and helped the investigations in medical aspects of sperm activity. As sperm chemotaxis draws more and more interest in fertilization research, the studies on sperm-egg communication may help to explain male or female infertility and provide exciting new approaches to contraception. However, single spot laser trapping can only be used to investigate an individual target, which has limits in efficiency and throughput. To study the chemotactic response of sperm to eggs and to characterize sperm motility, an annular laser trap with a diameter of several hundred microns is designed, simulated with ray tracing tool, and implemented. An axicon transforms the wavefront such that the laser beam is incident on the microscope objective from all directions while filling the back aperture completely for high efficiency trapping. A trapping experiment with microspheres is carried out to evaluate the system performance. The power requirement for annular sperm trapping is determined experimentally and compared with theoretical calculations. With a chemo-attractant located in the center and sperm approaching from all directions, the annular laser trapping could serve as a speed bump for sperm so that motility characterization and fertility sorting can be performed efficiently.

A diameter-adjustable annular laser trapping system based on axicons was designed for sperm chemotactaxis and fertilizability characterization. Experiment on microspheres testified the feasibility and performance of the system and was consistent with theoretical expectation. © 2005 Optical Society of America.

Osmanlı maarifinin modernleşme sürecinin en önemli eksikliklerinden biri de çağın gerektirdiği donanımda muallimlerin yeterince bulunmamasıydı. Bu açığın giderilmesi için 1848 yılında darülmualliminler açılmaya başlanmıştır. Zamanla vilayet merkezlerinde sayıları artan bu okullar bazı liva merkezlerinde de tesis edilmiştir. Bu süreçte Ayıntab’da açılmış olan darülmuallimin mektebi her ne kadar kısa bir süre hayatiyetini devam ettirmiş olsa da Ayıntab eğitim tarihi açısından önemli bir eğitim kurumudur. Zira mektebin tarihçesinin yanında Halep Maarif Müdüriyeti ile mektep personeli arasında yaşananlar ve yapılan tahkikat maarif dünyasının farklı bir yönünü ortaya koymaktadır. Bu çalışmada Ayıntab Darülmuallimininin açılış süreci, muallim tayinleri, mektebin kapatılması sürecindeki bürokratik işleyişin yanında yapılan tahkikatlar çerçevesinde maarif bürokrasisi ile mektep personeli arasındaki ilişki ele alınmıştır. Mektebin kapatılmasında livalardaki darülmualliminlere ödenek ayrılmamasının yanında Halep maarif bürokrasisi ile mektep personeli arasındaki gerginliğin mektep eğitimine yansımaları etkili olmuştur.

Some cancer cells rely heavily on non-essential biomolecules for survival, growth, and proliferation. Enzyme based therapeutics can eliminate these biomolecules, thus specifically targeting neoplastic cells; however, enzyme therapeutics are susceptible to immune clearance, exhibit short half-lives, and require frequent administration. Encapsulation of therapeutic cargo within biocompatible and biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) is a strategy for controlled release. Unfortunately, PLGA NPs exhibit burst release of cargo shortly after delivery or upon introduction to aqueous environments where they decompose via hydrolysis. Here, we show the generation of hybrid silica-coated PLGA (SiLGA) NPs as viable drug delivery vehicles exhibiting sub-200 nm diameters, a metastable Zeta potential, and high loading efficiency and content. Compared to uncoated PLGA NPs, SiLGA NPs offer greater retention of enzymatic activity and slow the burst release of cargo. Thus, SiLGA encapsulation of therapeutic enzymes, such as asparaginase, could reduce frequency of administration, increase half-life, and improve efficacy for patients with a range of diseases. [ABSTRACT FROM AUTHOR]

We present an optical spatial filtering device that has been integrated into a microfluidic system and whose motion and alignment is controlled using a laser optical tweezer. The lithographically patterned micro-optical spatial filter device filters out higher frequency additive noise components by automatically aligning itself in three dimensions to the focus of the laser beam. This serf-alignment capability is achieved through the attachment of a refractive optical element directly over the circular aperture or pinhole of the spatial filter. A discussion of two different spatial filter designs is presented along with experimental results that demonstrate the effectiveness of the serf-aligned micro-optic spatial filter. OCIS codes: 070.6110, 220.1140, 080.3620, 110.4280.

We present an overview of the properties and applications of optical bistability in vertical-cavity semiconductor optical amplifiers (VCSOAs). The basic physics and analytical models of this optical nonlinearity are discussed. Experimental results obtained from a VCSOA operated in the 850 nm wavelength region are presented. Counterclockwise hysteresis loops are obtained over a range of initial phase detuning and bias currents. One hysteresis loop is observed experimentally with an input power as low as 2 [mu]W when the device is biased at 98% of its lasing threshold. Numerical simulations based on the Fabry-Perot resonator model and rate equations we developed show good agreement with our experimental observations. In addition, a low input intensity high contrast (10:1) optical AND gate and 2R regeneration are demonstrated. We believe that bistable VCSOAs can significantly advance the prospect of a dense two-dimensional array of low-switching-intensity all-optical logic and memory elements. OCIS codes: 190.1450, 200.4660, 250.5980, 230.4320, 190.5970.

System-level packaging is one of the critical issues that need to be addressed for free space optical interconnections (FSOI) to become useful in desktop systems. The performance of FSOI, e.g., in terms of system bit-error rate, is greatly affected by misalignments in the optical system. Therefore tolerancing, i.e., the ability to analyze and predict the effects of misalignments in the system, is of prime importance to system designers. We introduce an approach in which we study the effects of optical misalignments and other tolerance factors using statistical methods. We use Monte Carlo simulations, design of the experiments, and regression techniques to fit a polynomial equation that expresses the relationship between the system performance and the tolerance factors. This prediction model can be used for design, cost optimization, and quality control purposes. In addition, we perform a sensitivity analysis to determine those tolerance variables that have the greatest effect on system performance. OCIS codes: 220, 0220, 230.0230, 250.0250, 000.5490, 060.4510, 120.4820.

We present a demonstration system under the three-dimensional (3D) optoelectronic stacked processor consortium. The processor combines the advantages of optics in global, high-density, high-speed parallel interconnections with the density and computational power of 3D chip stacks. In particular, a compact and scalable optoelectronic switching system with a high bandwidth is designed. The system consists of three silicon chip stacks, each integrated with a single vertical-cavity-surface-emitting-laser--metal-semiconductor-metal detector array and an optical interconnection module. Any input signal at one end stack can be switched through the central crossbar stack to any output channel on the opposite end stack. The crossbar bandwidth is designed to be 256 Gb/s. For the free-space optical interconnection, a novel folded hybrid micro--macro optical system with a concave reflection mirror has been designed. The optics module can provide a high resolution, a large field of view, a high link efficiency, and low optical cross talk. It is also symmetric and modular. Off-the-shelf macro-optical components are used. The concave reflection mirror can significantly improve the image quality and tolerate a large misalignment of the optical components, and it can also compensate for the lateral shift of the chip stacks. Scaling of the macrolens can be used to adjust the interconnection length between the chip stacks or make the system more compact. The components are easy to align, and only passive alignment is required. Optics and electronics are separated until the final assembly step, and the optomechanic module can be removed and replaced. By use of 3D chip stacks, commercially available optical components, and simple passive packaging techniques, it is possible to achieve a high-performance optoelectronic switching system. OCIS codes: 200.0200; 200.4650; 200.4960; 200.2610.