Targeting survivin for cancer therapy: Strategies, small molecule inhibitors and vaccine based therapeutics in development.

Survivin is a member of the family of inhibitors of apoptosis proteins (IAPs). It is involved in the normal mitotic process and acts as an anti-apoptotic molecule. While terminally differentiated normal tissues lack survivin, several human malignancies have significant protein levels. Resistance to chemotherapy and radiation in tumor cells is associated with survivin expression. Decreased tumor development, apoptosis, and increased sensitivity to chemotherapy and radiation are all effects of downregulating survivin expression or activity. As a prospective cancer treatment, small molecules targeting the transcription and translation of survivin and molecules that can directly bind with the survivin are being explored both in pre-clinical and clinics. Pre-clinical investigations have found and demonstrated the effectiveness of several small-molecule survivin inhibitors. Unfortunately, these inhibitors have also been shown to have off-target effects, which could limit their clinical utility. In addition to small molecules, several survivin peptide vaccines are currently under development. These vaccines are designed to elicit a cytotoxic T-cell response against survivin, which could lead to the destruction of tumor cells expressing survivin. Some survivin-based vaccines are advancing through Phase II clinical studies. Overall, survivin is a promising cancer drug target. However, challenges still need to be addressed before the survivin targeted therapies can be widely used in the clinics.

Acousto-optic modulator-based improvement in imaging through scattering media.

Reduced visibility is a common problem when light traverses through a scattering medium, and it becomes difficult to identify an object in such scenarios. What we believe to be a novel proof-of-principle technique for improving image visibility based on the quadrature lock-in discrimination algorithm in which the demodulation is performed using an acousto-optic modulator is presented here. A significant improvement in image visibility is achieved using a series of frames. We have also performed systematic imaging by varying the camera parameters, such as exposure time, frame rate, and series length, to investigate their effect on enhancing image visibility.

An all-optical technique enables instantaneous single-shot demodulation of images at high frequency.

High-frequency demodulation of wide area optical signals in a snapshot manner remains a technological challenge. If solved, it could open tremendous perspectives in 3D imaging, vibrometry, free-space communications, automated vision, or ballistic photon imaging in scattering media with numerous applications in smart autonomous vehicles and medical diagnosis. We present here a snapshot quadrature demodulation imaging technique, capable of estimating the amplitude and phase from a single acquisition, without synchronization of emitter and receiver, and with the added capability of continuous frequency tuning. This all-optical optimized setup comprises an electro-optic crystal acting as a fast sinusoidal optical transmission gate, and allows four quadrature image channels to be recorded simultaneously with any conventional camera. We report the design, experimental validation and examples of applications of such wide-field quadrature demodulating system that allowed snapshot demodulation of images with good spatial resolution and continuous frequency selectivity up to a few 100s of kilohertz.

Correction to: Cupriavidus malaysiensis sp. nov., a novel poly(3-hydroxybutyrate-co-4-hydroxybutyrate) accumulating bacterium isolated from the Malaysian environment.

In the original publication of the article, it was noted that Fig. 1 present an image of Cupriavidus malaysiensis strain USMAHM13 and not of strain USMAA1020, as indicated in the figure legend. The image in the original version is thus noted to serve as a record of strain USMAHM13 and the corrected version of Fig. 1 is reprinted below.

Cupriavidus malaysiensis sp. nov., a novel poly(3-hydroxybutyrate-co-4-hydroxybutyrate) accumulating bacterium isolated from the Malaysian environment.

Bacterial classification on the basis of a polyphasic approach was conducted on three poly(3 hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] accumulating bacterial strains that were isolated from samples collected from Malaysian environments; Kulim Lake, Sg. Pinang river and Sg. Manik paddy field. The Gram-negative, rod-shaped, motile, non-sporulating and non-fermenting bacteria were shown to belong to the genus Cupriavidus of the Betaproteobacteria on the basis of their 16S rRNA gene sequence analyses. The sequence similarity value with their near phylogenetic neighbour, Cupriavidus pauculus LMG3413T, was 98.5%. However, the DNA-DNA hybridization values (8-58%) and ribotyping analysis both enabled these strains to be differentiated from related Cupriavidus species with validly published names. The RiboPrint patterns of the three strains also revealed that the strains were genetically related even though they displayed a clonal diversity. The major cellular fatty acids detected in these strains included C15:0 ISO 2OH/C16:1 ω7c, hexadecanoic (16:0) and cis-11-octadecenoic (C18:1 ω7c). Their G+C contents ranged from 68.0  to 68.6 mol%, and their major isoprenoid quinone was Ubiquinone Q-8. Of these three strains, only strain USMAHM13 (= DSM 25816 = KCTC 32390) was discovered to exhibit yellow pigmentation that is characteristic of the carotenoid family. Their assembled genomes also showed that the three strains were not identical in terms of their genome sizes that were 7.82, 7.95 and 8.70 Mb for strains USMAHM13, USMAA1020 and USMAA2-4, respectively, which are slightly larger than that of Cupriavidus necator H16 (7.42 Mb). The average nucleotide identity (ANI) results indicated that the strains were genetically related and the genome pairs belong to the same species. On the basis of the results obtained in this study, the three strains are considered to represent a novel species for which the name Cupriavidus malaysiensis sp. nov. is proposed. The type strain of the species is USMAA1020T (= DSM 19416T = KCTC 32390T).

Measurements of spin properties of atomic systems in and out of equilibrium via noise spectroscopy.

We explore the applications of spin noise spectroscopy (SNS) for detection of the spin properties of atomic ensembles in and out of equilibrium. In SNS, a linearly polarized far-detuned probe beam on passing through an ensemble of atomic spins acquires the information of the spin correlations of the system which is extracted using its time-resolved Faraday-rotation noise. We measure various atomic, magnetic and sub-atomic properties as well as perform precision magnetometry using SNS in rubidium atomic vapor in thermal equilibrium. Thereafter, we manipulate the relative spin populations between different ground state hyperfine levels of rubidium by controlled optical pumping which drives the system out of equilibrium. We then apply SNS to probe such spin imbalance non-perturbatively. We further use this driven atomic vapor to demonstrate that SNS can have better resolution than typical absorption spectroscopy in detecting spectral lines in the presence of various spectral broadening mechanisms.

Complete Genome Sequences of Three Cupriavidus Strains Isolated from Various Malaysian Environments.

Cupriavidus sp. USMAA1020, USMAA2-4, and USMAHM13 are capable of producing polyhydroxyalkanoate (PHA). This biopolymer is an alternative solution to synthetic plastics, whereby polyhydroxyalkanoate synthase is the key enzyme involved in PHA biosynthesis. Here, we report the complete genomes of three Cupriavidus sp. strains: USMAA1020, USMAA2-4, and USMAHM13.

Enhanced production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymer and antimicrobial yellow pigmentation from Cupriavidus sp. USMAHM13 with antibiofilm capability.

Antibiofilm polymers have the ability to inhibit bacterial biofilm formation, which is known to occur ubiquitously in the environment and pose risks of infection. In this study, production of P(3HB-co-4HB) copolymer and antimicrobial yellow pigment from Cupriavidus sp. USMAHM13 are enhanced through medium optimization. Before the improvement of yellow pigment production, screening for the best additional supplement was performed resulting in high-yield yellow pigmentation using yeast extract with optimum concentration of 2 g/L. Effects of different concentrations of 1,4-butanediol, ammonium acetate, and yeast extract were studied using central composite design. Under optimal conditions, 53 wt% of polyhydroxyalkanoate (PHA) content, 0.35 g/L of pigment concentration, and 5.87 g/L of residual biomass were achieved at 0.56 wt% C of 1,4-butanediol, 1.14 g/L of ammonium acetate, and 2 g/L of yeast extract. Antibiofilm tests revealed that the yellow pigment coated on P(3HB-co-4HB) copolymer had significant effect on the inhibition of bacteria proliferation and colonization from 6 hr onward reaching 100% inhibition by 12 hr, hence effectively inhibiting the biofilm formation.

Theoretical optimal modulation frequencies for scattering parameter estimation and ballistic photon filtering in diffusing media.

The efficiency of using intensity modulated light for the estimation of scattering properties of a turbid medium and for ballistic photon discrimination is theoretically quantified in this article. Using the diffusion model for modulated photon transport and considering a noisy quadrature demodulation scheme, the minimum-variance bounds on estimation of parameters of interest are analytically derived and analyzed. The existence of a variance-minimizing optimal modulation frequency is shown and its evolution with the properties of the intervening medium is derived and studied. Furthermore, a metric is defined to quantify the efficiency of ballistic photon filtering which may be sought when imaging through turbid media. The analytical derivation of this metric shows that the minimum modulation frequency required to attain significant ballistic discrimination depends only on the reduced scattering coefficient of the medium in a linear fashion for a highly scattering medium.

Real-time imaging through strongly scattering media: seeing through turbid media, instantly.

Numerous everyday situations like navigation, medical imaging and rescue operations require viewing through optically inhomogeneous media. This is a challenging task as photons propagate predominantly diffusively (rather than ballistically) due to random multiple scattering off the inhomogenieties. Real-time imaging with ballistic light under continuous-wave illumination is even more challenging due to the extremely weak signal, necessitating voluminous data-processing. Here we report imaging through strongly scattering media in real-time and at rates several times the critical flicker frequency of the eye, so that motion is perceived as continuous. Two factors contributed to the speedup of more than three orders of magnitude over conventional techniques - the use of a simplified algorithm enabling processing of data on the fly, and the utilisation of task and data parallelization capabilities of typical desktop computers. The extreme simplicity of the technique, and its implementation with present day low-cost technology promises its utility in a variety of devices in maritime, aerospace, rail and road transport, in medical imaging and defence. It is of equal interest to the common man and adventure sportsperson like hikers, divers, mountaineers, who frequently encounter situations requiring realtime imaging through obscuring media. As a specific example, navigation under poor visibility is examined.

Identification and characterization of the yellow pigment synthesized by Cupriavidus sp. USMAHM13.

Microbial pigments are gaining intensive attention due to increasing awareness of the toxicity of synthetic colours. In this study, a novel polymer-producing bacterium designated as Cupriavidus sp. USMAHM13 was also found to produce yellow pigment when cultivated in nutrient broth. Various parameters such as temperature, pH and ratio of culture volume to flask volume were found to influence the yellow pigment production. UV-Visible, Fourier transform infrared and (13)C-nuclear magnetic resonance analyses revealed that the crude yellow pigment might probably represent new bioactive compound in the carotenoid family. The crude yellow pigment also exhibited a wide spectrum of antimicrobial activity against Gram-negative and Gram-positive bacteria with their inhibition zones and minimal inhibitory concentrations ranged from 25 to 38 mm and from 0.63 to 2.5 mg/ml, respectively. To the best of our knowledge, this is the first report on the identification and characterization of yellow pigment produced by bacterium belonging to the genus Cupriavidus.

Long-range polarimetric imaging through fog.

We report an experimental implementation of long-range polarimetric imaging through fog over kilometric distance in real field atmospheric conditions. An incoherent polarized light source settled on a telecommunication tower is imaged at a distance of 1.3 km with a snapshot polarimetric camera including a birefringent Wollaston prism, allowing simultaneous acquisition of two images along orthogonal polarization directions. From a large number of acquisitions datasets and under various environmental conditions (clear sky/fog/haze, day/night), we compare the efficiency of using polarized light for source contrast increase with different signal representations (intensity, polarimetric difference, polarimetric contrast, etc.). With the limited-dynamics detector used, a maximum fourfold increase in contrast was demonstrated under bright background illumination using polarimetric difference image.

Bioconversion of glycerine pitch into a novel yellow-pigmented P(3HB-co-4HB) copolymer: synergistic effect of ammonium acetate and polymer characteristics.

Glycerine pitch waste generated from oleochemical industry was exploited as a carbon source for poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB)) copolymer production by a novel, yellow-pigmented bacterium Cupriavidus sp. USMAHM13 to improve the economics of microbial polyhydroxyalkanoate production and to establish a feasible waste management approach. Medium optimization using response surface methodology through shake-flask fermentation had led to the accumulation of P(3HB-co-51%4HB) copolymer using a combination of glycerine pitch (10 g/l), 1,4-butanediol (8.14 g/l), and ammonium acetate (2.39 g/l). P(3HB-co-4HB) copolymers with 4HB monomer compositions ranged from 3 to 40 mol% were obtained through batch fermentation in a bioreactor using different concentrations of ammonium acetate. The copolymers exhibited a wide range of material properties depending on the monomer composition and type of carbon sources. P(3HB-co-40%4HB) was a typical random copolymer, whereas other P(3HB-co-4HB) produced were blend copolymers. Carotenoid pigment which was produced simultaneously with the polymer production was found to have negligible effect on the mechanical and thermal properties of the P(3HB-co-4HB) copolymer films.

Optical phase noise engineering via acousto-optic interaction and its interferometric applications.

Rapid and fine control over the phase of light is demonstrated by transferring digitally generated phase jumps from radio-frequency electrical signals onto light by means of acousto-optic interaction, and the underlying mechanism elucidated. This technique was used to engineer optical phase noise by tailoring the statistics of phase jumps in the electrical signal, which was then quantified using visibility measurements of the interference fringes. Such controlled dephasing finds applications in modern experiments involving the spread or diffusion of light in optical networks. In addition, the zero-delay intensity-intensity correlation [G2(0)] values of light emerging from different ports of a well-stabilized Mach-Zehnder interferometer in the presence of engineered partial phase noise are calculated, and it is shown analytically how the dark port of the interferometer nontrivially becomes a weak source of highly correlated or bunched photons.

Biosynthesis and characterization of poly (3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxybutyrate) terpolymer with various monomer compositions by Cupriavidus sp. USMAA2-4.

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-4-hydroxybutyrate) [P(3HB-co-3HV-co-4HB)] terpolymer was produced using Cupriavidus sp. USMAA2-4 via one-step cultivation process through combination of various carbon sources such as 1,4-butanediol or γ-butyrolactone with either 1-pentanol, valeric acid, or 1-propanol. Oleic acid was added to increase the biomass production. The composition of 3HV and 4HB monomers were greatly affected by the concentration of 1,4-butanediol and 1-pentanol. Terpolymers with 3HV and 4HB molar fractions ranging from 2 to 41 mol.% and 5 to 31 mol.%, respectively, were produced by varying the concentration of carbon precursors. The thermal and mechanical properties of the terpolymers containing different proportions of the constituent monomers were characterized using gel permeation chromatography (GPC), DSC, and tensile machine. GPC analysis showed that the molecular weights (M (w)) of the terpolymer produced were within the range of 346 to 1,710 kDa. The monomer compositions of 3HV and 4HB were also found to have great influences on the thermal and mechanical properties of the terpolymer P(3HB-co-3HV-co-4HB) produced.

Optical-tweezer-induced microbubbles as scavengers of carbon nanotubes.

A modified optical tweezers set-up has been used to generate microbubbles in flowing, biologically relevant fluids and human whole blood that contains carbon nanotubes (CNTs) using low power (< or =5 mW), infrared (1064 nm wavelength), continuous wave laser light. Temperature driven effects at the tweezers' focal point help to optically trap these microbubbles. It is observed that proximate CNTs are driven towards the focal spot where, on encountering the microbubble, they adhere to it. Such CNT-loaded microbubbles can be transported both along and against the flow of surrounding fluid, and can also be exploded to cause fragmentation of the bundles. Thus, microbubbles may be used for scavenging, transporting and dispersal of potentially toxic CNTs in biologically relevant environments.

Bright visible emission from carbon nanotubes spatially constrained on a micro-bubble.

We report emission of broadband light in the spectral range 500 nm - 900 nm from single walled carbon nanotubes (SWNTs) in a liquid environment upon irradiance by a very low power (typically <5 mW), continuous-wave laser source in a tweezers setup. We show (i) formation of micro-bubbles upon irradiation of fluids containing bundles of SWNTs, (ii) optical trapping of such micro-bubbles, (iii) adhesion of SWNTs on the surface of such micro-bubbles, and (iv) bright emission of white light due to tweezer-induced localized heating of spatially-constrained SWNTs.

Evanescent-wave-excited quasi-two-dimensional random lasing.

We report on random lasing from a dye-scatterer system directly excited by evanescent modes formed over a dielectric-dielectric interface. The system is quasi-two-dimensional because of the subwavelength exponential decay of the excitation energy. Spectral narrowing by a factor of approximately 13 was obtained under diffusive scattering conditions. The peak intensity exhibited a unique dual-saturation behavior due to the localized nature of the excitation. We observed a reduction of threshold for samples with a higher dye concentration because of a larger excitation-state occupation number within the same interaction volume.

Lévy statistics of emission from a novel random amplifying medium: an optical realization of the Arrhenius cascade.

We report the observation of Lévy-like statistical configuration-to-configuration fluctuations in the intensity of emission from a novel system, the fiber-random amplifying medium, where active fiber segments are embedded randomly in a bulk of pointlike passive scatterers. Some rare configurations of fibers provide long, guided amplifying paths for the photons, leading to high jumps in the intensity, and thus to Lévy statistics. This system provides an optical realization of the Arrhenius cascade.