Functional imaging through scattering medium via fluorescence speckle demixing and localization.

Recently, fluorescence-based optical techniques have emerged as a powerful tool to probe information in the mammalian brain. However, tissue heterogeneities prevent clear imaging of deep neuron bodies due to light scattering. While several up-to-date approaches based on ballistic light allow to retrieve information at shallow depths inside the brain, non-invasive localization and functional imaging at depth still remains a challenge. It was recently shown that functional signals from time-varying fluorescent emitters located behind scattering samples could be retrieved by using a matrix factorization algorithm. Here we show that the seemingly information-less, low-contrast fluorescent speckle patterns recovered by the algorithm can be used to locate each individual emitter, even in the presence of background fluorescence. We test our approach by imaging the temporal activity of large groups of fluorescent sources behind different scattering phantoms mimicking biological tissues, and through a brain slice with a thickness of ∼200 µm.

Functional imaging through scattering medium via fluorescence speckle demixing and localization.

Recently, fluorescence-based optical techniques have emerged as a powerful tool to probe information in the mammalian brain. However, tissue heterogeneities prevent clear imaging of deep neuron bodies due to light scattering. While several up-to-date approaches based on ballistic light allow to retrieve information at shallow depths inside the brain, non-invasive localization and functional imaging at depth still remains a challenge. It was recently shown that functional signals from time-varying fluorescent emitters located behind scattering samples could be retrieved by using a matrix factorization algorithm. Here we show that the seemingly information-less, low-contrast fluorescent speckle patterns recovered by the algorithm can be used to locate each individual emitter, even in the presence of background fluorescence. We test our approach by imaging the temporal activity of large groups of fluorescent sources behind different scattering phantoms mimicking biological tissues, and through a brain slice with a thickness of ~200 micron.

Curved Beam Computed Tomography based Structural Rigidity Analysis of Bones with Simulated Lytic Defect: A Comparative Study with Finite Element Analysis.

In this paper, a CT based structural rigidity analysis (CTRA) method that incorporates bone intrinsic local curvature is introduced to assess the compressive failure load of human femur with simulated lytic defects. The proposed CTRA is based on a three dimensional curved beam theory to obtain critical stresses within the human femur model. To test the proposed method, ten human cadaveric femurs with and without simulated defects were mechanically tested under axial compression to failure. Quantitative computed tomography images were acquired from the samples, and CTRA and finite element analysis were performed to obtain the failure load as well as rigidities in both straight and curved cross sections. Experimental results were compared to the results obtained from FEA and CTRA. The failure loads predicated by curved beam CTRA and FEA are in agreement with experimental results. The results also show that the proposed method is an efficient and reliable method to find both the location and magnitude of failure load. Moreover, the results show that the proposed curved CTRA outperforms the regular straight beam CTRA, which ignores the bone intrinsic curvature and can be used as a useful tool in clinical practices.

Protocol for constructing subject-specific biomechanical models of knee joint.

A robust protocol for building subject-specific biomechanical models of the human knee joint is proposed which uses magnetic resonance imaging, motion analysis and force platform data in conjunction with detailed 3D finite element models. The proposed protocol can be used for determining stress and strain distributions and contact kinetics in different knee elements at different body postures during various physical activities. Several examples are provided to highlight the capabilities and potential applications of the proposed protocol. This includes preliminary results on the role of body weight on the stresses and strains induced in the knee articular cartilages and meniscus during single-leg stance and calculations of the induced stresses and ligament forces during the gait cycle.

Computational model of rib movement and its application in studying the effects of age-related thoracic cage calcification on respiratory system.

A 3D finite element model of rib cage movement is developed and used to study the role of age-related costal cartilage and sternocostal joint calcification, as well as respiratory muscle weakness on the 'bucket-handle' movement of human rib. The volume displacement of the rib cage is related to changes in its circumference using an empirical equation presented by Agostoni et al. (1965, J Appl Physiol, 20:1179-1186). A systematic study is carried out to quantify the role of costal cartilage, sternocostal joint calcification and muscle weakness on the volume displacement of the rib cage. The results provide insight into some of the mechanisms underlying age-related changes in the respiratory system.

Quantized rotation of atoms from photons with orbital angular momentum.

We demonstrate the coherent transfer of the orbital angular momentum of a photon to an atom in quantized units of variant Planck's over 2pi, using a 2-photon stimulated Raman process with Laguerre-Gaussian beams to generate an atomic vortex state in a Bose-Einstein condensate of sodium atoms. We show that the process is coherent by creating superpositions of different vortex states, where the relative phase between the states is determined by the relative phases of the optical fields. Furthermore, we create vortices of charge 2 by transferring to each atom the orbital angular momentum of two photons.

High-order quantum resonances observed in a periodically kicked Bose-Einstein condensate.

We have observed high-order quantum resonances in a realization of the quantum delta-kicked rotor, using Bose-condensed Na atoms subjected to a pulsed standing wave of laser light. These resonances occur for pulse intervals that are rational fractions of the Talbot time, and are characterized by ballistic momentum transfer to the atoms. The condensate's narrow momentum distribution not only permits the observation of the quantum resonances at 3/4 and 1/3 of the Talbot time, but also allows us to study scaling laws for the resonance width in quasimomentum and pulse interval.

Superficial wrinkles in stretched, drying gelatin films.

When a thin film of initially hydrated gelatin is allowed to dry from the surface, superficial changes in the structure of the material affect the local mechanical properties of the drying region. If the film is simultaneously subjected to large strain deformation (above 20%), a periodic pattern of wrinkles appears on the surface of the gelatin along the length of the sample in the direction of the applied force. These wrinkles are uniformly distributed on the surface of the gelatin with a wavelength that is much smaller than the sample thickness, which changes with sample composition, aging time, and deformation rate. We investigate these patterns via in situ environmental scanning electron microscopy (ESEM) and provide a theory for their origin.

Experimental quantum coin tossing.

In this Letter we present the first implementation of a quantum coin-tossing protocol. This protocol belongs to a class of "two-party" cryptographic problems, where the communication partners distrust each other. As with a number of such two-party protocols, the best implementation of the quantum coin tossing requires qutrits, resulting in a higher security than using qubits. In this way, we have also performed the first complete quantum communication protocol with qutrits. In our experiment the two partners succeeded to remotely toss a row of coins using photons entangled in the orbital angular momentum. We also show the experimental bounds of a possible cheater and the ways of detecting him.

Triggered qutrits for quantum communication protocols.

A general protocol in quantum information and communication relies in the ability of producing, transmitting, and reconstructing, in general, qunits. In this Letter we show for the first time the experimental implementation of these three basic steps on a pure state in a three-dimensional space, by means of the orbital angular momentum of the photons. The reconstruction of the qutrit is performed with tomographic techniques and a maximum-likelihood estimation method. For the tomographic reconstruction we used more than 2400 different projections. In this way we also demonstrate that we can perform any transformation in the three-dimensional space.

Entanglement of the orbital angular momentum states of photons.

Entangled quantum states are not separable, regardless of the spatial separation of their components. This is a manifestation of an aspect of quantum mechanics known as quantum non-locality. An important consequence of this is that the measurement of the state of one particle in a two-particle entangled state defines the state of the second particle instantaneously, whereas neither particle possesses its own well-defined state before the measurement. Experimental realizations of entanglement have hitherto been restricted to two-state quantum systems, involving, for example, the two orthogonal polarization states of photons. Here we demonstrate entanglement involving the spatial modes of the electromagnetic field carrying orbital angular momentum. As these modes can be used to define an infinitely dimensional discrete Hilbert space, this approach provides a practical route to entanglement that involves many orthogonal quantum states, rather than just two Multi-dimensional entangled states could be of considerable importance in the field of quantum information, enabling, for example, more efficient use of communication channels in quantum cryptography.

Mitochondrial DNA and chromosomal studies of wild mice (Mus) from Turkey and Iran.

Complete D-loop sequences of 20 Mus from three localities in Turkey and seven in Iran were characterized. These countries are thought to be close to the place of origin of the subspecies Mus musculus domesticus. Five new M. m. domesticus haplotypes were added to the nine already known for the region. Four of these 14 haplotypes were very similar to the consensus D-loop sequence for western Europe defined by Nachman et al. (1994), which may represent the ancestral condition for M. m. domesticus. A divergent mtDNA lineage is found in various parts of Turkey and northern Iran; it has spread into western Europe, but other European lineages were not found in either Turkey or Iran. The other Mus D-loop sequences were of M. m. castaneus and Mus macedonicus and confirmed M. macedonicus as a monotypic species with low nucleotide diversity. The prevalence of the standard 40-chromosome complement in this region is particularly interesting with regards M. m. domesticus, as it is consistent with the in situ origin of Robertsonian karyotypic races (2n < 40) in western Europe.

Is there an optimal time to measure quantitative HCV RNA to predict non-response following interferon treatment for chronic HCV infection?

BACKGROUND/AIMS: Current criteria to predict sustained response for a patient with chronic hepatitis C virus during interferon treatment are not consistent. The aim of this study was to determine a reliable point in time to predict non-response to therapy, as a theoretical basis for early cessation of treatment. METHODS: Sera (-70 degrees C) from 66 patients treated with interferon (3 million units three times a week for 6 months) were assayed with a quantitative polymerase chain reaction (sensitivity < or =100 copies per milliliter). Evaluations were made at baseline, during treatment at weeks 1, 2, 4, 12, and 24, and at follow-up week 48. Biochemical response was defined using standard alanine aminotransferase criteria. Virologic response was defined as: sustained if loss of HCV RNA persisted through therapy and follow-up; relapse if HCV RNA became undetectable but reappeared during treatment or follow-up; and non-response if HCV RNA remained detectable during the study period. Alanine aminotransferase and HCV RNA results were analyzed at defined time intervals to determine a predictive value for non-response and sustained response. RESULTS: HCV RNA results are a more accurate predictor than alanine aminotransferase for both non-response and sustained response. Serum HCV RNA predicted non-response better than sustained response. The optimal time to predict non-response with serum HCV RNA was treatment week 12. CONCLUSIONS: Treatment week 12 results indicate that HCV RNA was a more accurate predictor for non-response than serum alanine aminotransferase. This prediction would have theoretically permitted stopping treatment for 75% of the patients in this study at treatment week 12 allowing an overall cost savings of 28%.

Portal decompression by transjugular intrahepatic portosystemic shunt and changes in serum-ascites albumin gradient.

The serum ascites albumin gradient (SAAG) is widely used to help determine the cause of ascites formation. A serum ascites albumin gradient of > or = 1.1 g/dL reliably distinguishes portal hypertension-related ascites from other causes. To date, there are no published data on the impact of portal decompression on this gradient. The recent development of transjugular intrahepatic portosystemic shunt (TIPS) allows for nonsurgical decompression of portal hypertension by radiologically creating a portosystemic shunt. This study examines the short-term impact of portal decompression on the serum ascites albumin gradient (SAAG) in patients with portal hypertension-related ascites undergoing transjugular intrahepatic portosystemic shunt. Portal pressure measurements were obtained before and after TIPS placement. Serum ascites albumin gradient was determined before and at 6 and 24 hours post-TIPS placement. Fifteen patients were enrolled in the study. The mean portosystemic gradient (PSG) before TIPS was 21.0 +/- 9.2 mmHg, whereas the post-TIPS mean PSG was reduced to 11.0 +/- 6.3 mmHg, consistent with portal decompression (p = 0.005). The mean pre-TIPS serum ascites albumin gradient was 1.9 +/- 0.5 g/dL and was reduced to 1.7 +/- 0.5 g/dL at 6 hours (p = 0.003) and 1.4 +/- 0.4 g/dL at 24 hours (p = 0.002) after TIPS placement. These findings further solidify the association between the SAAG and portal hypertension.

Hepatitis C and G co-infection: response to interferon therapy and quantitative changes in serum HGV-RNA.

Hepatitis G virus (HGV), a positive sense RNA virus, is distantly related to hepatitis C virus (HCV): its genetic organization and identity are consistent with the Flaviviridae family. Coinfection with HGV occurs in 10% to 20% of HCV-infected subjects. These similarities raise two theoretical questions. First, could HGV coinfection play any role in the response of HCV to antiviral therapy and second, would this coinfected population have changes in serum HGV-RNA induced by interferon. To address these questions, 98 patients with documented chronic HCV underwent interferon therapy (3 million units three times a week) for 6 months. Response to therapy was categorized using standard biochemical criteria. Changes in HGV-RNA levels were evaluated before, during, and after interferon therapy by a quantitative branched DNA amplification research-based assay. Eleven of 98 (11%) patients with HCV infection had detectable serum HGV-RNA. There was no difference between the groups (HGV+ vs. HGV-) when baseline alanine aminotransferase (ALT) values, HCV-RNA levels, HCV genotype, histological severity, or other demographic features were analyzed. Interferon response was similar in both groups and HGV was not associated with outcome following therapy. Antiviral therapy appeared to induce a reduction in HGV-RNA load in five of nine patients coinfected with HCV serially tested. In two patients, the fall in serum HGV-RNA correlated with biochemical response, independent of changes in HCV-RNA. These observations indicate that a larger study of an HGV population is required to more clearly define the relationship between HCV and HGV coinfection and their response to antiviral therapy.

Fluctuations in viral load (HCV RNA) are relatively insignificant in untreated patients with chronic HCV infection.

A recently available assay to quantify serum viral load in hepatitis C virus (HCV) infection has been used to evaluate the effects of anti-viral therapies. However, variability in HCV RNA levels in untreated patients with HCV infection has not yet been established. We therefore prospectively measured the biological fluctuations of HCV RNA in sera from untreated patients with chronic HCV infection. Sera were collected from seven patients at 8 am and 4 pm on the same day to assess the effect of diurnal variation, daily for 5 days in a further 10 patients, biweekly for 6 weeks in nine patients and monthly for 3 months in 11 patients. All patients had biopsy-proven chronic liver disease with elevated alanine aminotransferase (ALT) values and had not received anti-viral treatment. HCV RNA was measured blinded, in duplicate, using the quantitative branched (bDNA) amplification assay (Quantiplex HCV RNA, Chiron Co. Emeryville, CA) 36 of the 37 patients studied had measurable HCV RNA throughout the study. There was no significant correlation between HCV RNA levels and ALT values or histological activity. HCV RNA levels did not appear to vary significantly within any of the groups studied and there did not appear to be a change associated with diurnal variation. All individual patients demonstrated less than a threefold fluctuation in HCV RNA throughout the study period. Hence HCV RNA levels remain relatively stable in untreated individuals with chronic HCV infection. Changes of a magnitude of threefold (0.5 log) or greater in HCV RNA levels were not observed in untreated patients.

Improved stability of w/o/w multiple emulsions by addition of hydrophilic colloid components in the aqueous phases.

To improve the stability of w/o/w multiple emulsions of arachis and olive oil the stabilizing effect of cherry gum, in combination with acacia and gelatin, was examined. The outstanding film-forming properties of this gum having already been noted; the effect of its addition to the aqueous phases was measured by the coalescence of emulsion globules. The enhanced stability, as compared to controls, was achieved at a minimum concentration which liquid crystal-bearing interfacial films seem to appear. Creation of more coherent interfaces, inhibiting transfer of phases, could be the basis of the improved stability of the emulsion.

Some preparative variables influencing the properties of W/O/W multiple emulsions.

Water-in-oil-in-water multiple emulsions of chloroquine diphosphate were prepared, using olive oil, arachis oil, Span 80, gelatin, acacia and Tween 80. Emulsifiers were employed individually or in combination. An attempt was made to correlate preparative variables with stability and drug release of multiple emulsions of roughly comparative particle size. When the emulsions were satisfactorily stabilized by the optimum blend of surfactants the rate of release varied with the nature and/or combination of emulsifiers employed. The possible effects of phase-inversion temperature, spontaneous emulsification and liquid crystal stabilization on the systems have been discussed. The mechanism probably involved complex interfacial adsorption and hydrodynamic phenomena in the presence of natural oils, co-surfactants and natural stabilizers of individual HLB number, particularly when acacia is present in the system. This could be attributed to the existence of protein in some species of acacia, since there are about 130 species of acacia, the gummy exudations of which are considered official in compendia. The protein content could be a reasonable additional specification for acacia as an emulsifier.

Slow release of chloroquine phosphate from multiple taste-masked W/O/W multiple emulsions.

The efficacy and safety of chloroquine as an antimalarial has contributed to the survival of millions in the past 50 years. Chloroquine is widely available, cheap, well tolerated and orally well absorbed. Therefore, it remains an important antimalarial drug. However, on oral administration, particularly to children, the unpleasant taste is a problem. This could be avoided by 'taste-masked and controlled release' formulations such as multiple emulsions. Although Plasmodium falciparum has developed resistance to many antimalarial drugs, including chloroquine, resistance may be attributed, among other factors, to subclinical dosage of chloroquine from administered pharmaceutical forms. This could also be relevant in the treatment of rheumatoid arthritis. Multiple W/O/W emulsions of chloroquine phosphate were prepared. Assessment of emulsion stability showed no significant change in the system. Prolonged storage (four months) of the emulsion resulted in negligible loss of chloroquine phosphate. The results suggest, therefore, that chloroquine phosphate releases due to diffusion of the drug from the internal globules and not as a consequence of instability of the W/O/W emulsion. These characteristics are in accordance with the requirements for controlled release pharmaceuticals. Stability of multiple emulsions could have resulted from interfacial polymerization or complexion between molecules. Release assessments showed faster rates for W/O/W emulsions which had smaller internal aqueous globules and, therefore, an increased interfacial area. Furthermore, transport of high-diffusion coefficient micelles could have given a greater solute flux in these systems.