396 research outputs found
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Applications of Holographic Optical Tweezers: Multiplexed Fluorescence Spectroscopy and the Micromechanics of Type-I Collagen
The development and some applications of holographic optical tweezers (HOT) are presented. Our HOT system uses a spatial light modulator (SLM) to control the location and properties of the optical trap. We have developed a method for optimizing the diffraction efficiency of a SLM that can be applied in situ and addresses the issues of nonlinear phase modulation and phase modulation less than 2π. The method employs a one-dimensional blazed phase grating written on the SLM. For an ideal SLM, the phase shift is linear and covers 0-2π, yielding a first-order diffraction efficiency of unity. For a realistic SLM with nonlinear or reduced phase shift, the efficiency is approximately η =1 − σ², where σ² is the variance of the phase error from the ideal case. Because each pixel contributes to the phase error independently, this suggests a method to maximize the efficiency by adjusting the phase encoding of the SLM pixel-by-pixel. In practice, we do this by adjusting the gray-scale of each pixel while measuring the first-order diffracted power. The collection of optimal gray values comprises the optimized gray-scale lookup table, which exhibits the nonlinearity required to produce a linear phase grating and the saturated phase encoding that maximizes the efficiency of phase limited SLMs.
The optimized SLM enables strong trapping power, even when distributed among multiple traps, which is essential to enable our system to trap multiple nanosensors and simultaneously detect the sensors’ fluorescence spectra with an imaging spectrometer. Such nanosensors are capable of detecting changes in their environment such as pH, ion concentration, temperature, and voltage by monitoring changes in the nanosensors’ emitted fluorescence spectra. We have used streptavidin labeled quantum dots bound to the surface of biotin labeled polystyrene microspheres to measure temperature changes by observing a corresponding shift in the wavelength of the spectral peak, which is excited with a 532 nm wide field laser source. Particles with diameter greater than the wavelength of light exhibit Mie resonances in their fluorescence spectrum whose spectral locations are dependent on the size of the particle and the relative index of refraction between the particle and the surrounding medium.
HOT also provides a useful platform to study the micromechanical properties of elastic materials such as collagen. Collagen gels are widely used in experiments on cell mechanics because collagen is the most abundant protein in the mammalian extracellular matrix and is the primary source of its mechanical properties. Collagen gels are often approximated as homogeneous elastic materials; however, variations in the collagen fiber microstructure and cell adhesion forces cause the mechanical propertiesto be inhomogeneous at the cellular scale. We study the mechanics of type I collagen on the scale of tens to hundreds of microns by using HOT to apply picoNewton forces to micron-sized particles embedded in the collagen fiber network. We measure the local compliance and elastic modulus of the collagen network and find that particle displacements are inhomogeneous, anisotropic and asymmetric. Confocal reflection microscopy is used to reveal the local fiber structure and a simulation treating the network as a triangular lattice is used for comparison to the HOT measurements. Collagen samples prepared at 21◦C and 37◦C show that gels formed at lower temperature are more inhomogeneous, anisotropic, and compliant than those formed at high temperature, and cellularized samples allow us to characterize the effects of cell adhesion forces on the network mechanics
Reconstruction of 2D Al Ti on TiB in an aluminium melt
It has been widely considered that Al Ti is involved in the aluminium nucleation on TiB , although the mechanism has not been fully understood. In this paper molecular dynamics has been conducted to investigate this phenomenon at an atomistic scale. It was found that a two-dimensional Al Ti layer may remain on TiB above the aluminium liquidus. In addition, the results showed that this 2D Al Ti undergoes interface reconstruction by forming a triangular pattern. This triangular pattern consists of different alternative stacking sequences. The transition region between the triangles forms an area of strain concentration. By means of this mechanism, this interfacial Al Ti layer stabilizes itself by localizing the large misfit strain between TiB and Al Ti This reconstruction is similar to the hdp-fcc interface reconstruction in other systems which has been observed experimentally.EPSR
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General algorithm to optimize the diffraction efficiency of a phase-type spatial light modulator
We present a general approach for optimizing the diffraction efficiency of a phase-type spatial light modulator (SLM). While the SLM displays a one-dimensional phase grating, the phase shift of one pixel in the grating is varied and the first-order diffraction efficiency is measured. This is repeated pixel-by-pixel to find the optimum phase encoding for the device that maximizes the diffraction efficiency. This method compensates for nonlinearity of the modulator phase response and is especially useful for optimizing modulators with less than 2 π phase shift. (C) 2013 Optical Society of AmericaThis paper was published in Optics Letters and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://www.opticsinfobase.org/view_article.cfm?gotourl=http%3A%2F%2Fwww.opticsinfobase.org%2FDirectPDFAccess%2F8B6E409F-0B92-E94D-7E8B735148333EDA_259642%2Fol-38-15-2767.pdf%3Fda%3D1%26id%3D259642%26seq%3D0%26mobile%3Dno&org=Oregon%20State%20University. Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law.Keywords: Manipulation, Displa
International Variations in Surgical Morbidity and Mortality Post Gynaecological Oncology Surgery: A Global Gynaecological Oncology Surgical Outcomes Collaborative Led Study (GO SOAR1)
Gynaecological malignancies affect women in low and middle income countries (LMICs) at disproportionately higher rates compared with high income countries (HICs) with little known about variations in access, quality, and outcomes in global cancer care. Our study aims to evaluate international variation in post-operative morbidity and mortality following gynaecological oncology surgery between HIC and LMIC settings. Study design consisted of a multicentre, international prospective cohort study of women undergoing surgery for gynaecological malignancies (NCT04579861). Multilevel logistic regression determined relationships within three-level nested-models of patients within hospitals/countries. We enrolled 1820 patients from 73 hospitals in 27 countries. Minor morbidity (Clavien-Dindo I-II) was 26.5% (178/672) and 26.5% (267/1009), whilst major morbidity (Clavien-Dindo III-V) was 8.2% (55/672) and 7% (71/1009) for LMICs/HICs, respectively. Higher minor morbidity was associated with pre-operative mechanical bowel preparation (OR = 1.474, 95%CI = 1.054-2.061, p = 0.023), longer surgeries (OR = 1.253, 95%CI = 1.066-1.472, p = 0.006), greater blood loss (OR = 1.274, 95%CI = 1.081-1.502, p = 0.004). Higher major morbidity was associated with longer surgeries (OR = 1.37, 95%CI = 1.128-1.664, p = 0.002), greater blood loss (OR = 1.398, 95%CI = 1.175-1.664, p ≤ 0.001), and seniority of lead surgeon, with junior surgeons three times more likely to have a major complication (OR = 2.982, 95%CI = 1.509-5.894, p = 0.002). Of all surgeries, 50% versus 25% were performed by junior surgeons in LMICs/HICs, respectively. We conclude that LMICs and HICs were associated with similar post-operative major morbidity. Capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention
The DNA methylome of cervical cells can predict the presence of ovarian cancer
The vast majority of epithelial ovarian cancer arises from tissues that are embryologically derived from the Müllerian Duct. Here, we demonstrate that a DNA methylation signature in easy-to-access Müllerian Duct-derived cervical cells from women with and without ovarian cancer (i.e. referred to as the Women’s risk IDentification for Ovarian Cancer index or WID-OC-index) is capable of identifying women with an ovarian cancer in the absence of tumour DNA with an AUC of 0.76 and women with an endometrial cancer with an AUC of 0.81. This and the observation that the cervical cell WID-OC-index mimics the epigenetic program of those cells at risk of becoming cancerous in BRCA1/2 germline mutation carriers (i.e. mammary epithelium, fallopian tube fimbriae, prostate) further suggest that the epigenetic misprogramming of cervical cells is an indicator for cancer predisposition. This concept has the potential to advance the field of risk-stratified cancer screening and prevention
Methylation patterns in serum DNA for early identification of disseminated breast cancer
BACKGROUND: Monitoring treatment and early detection of fatal breast cancer (BC) remains a major unmet need.
Aberrant circulating DNA methylation (DNAme) patterns are likely to provide a highly specific cancer signal. We
hypothesized that cell-free DNAme markers could indicate disseminated breast cancer, even in the presence of
substantial quantities of background DNA.
METHODS: We used reduced representation bisulfite sequencing (RRBS) of 31 tissues and established serum assays
based on ultra-high coverage bisulfite sequencing in two independent prospective serum sets (n = 110). The clinical
use of one specific region, EFC#93, was validated in 419 patients (in both pre- and post-adjuvant chemotherapy
samples) from SUCCESS (Simultaneous Study of Gemcitabine-Docetaxel Combination adjuvant treatment, as well as
Extended Bisphosphonate and Surveillance-Trial) and 925 women (pre-diagnosis) from the UKCTOCS (UK Collaborative
Trial of Ovarian Cancer Screening) population cohort, with overall survival and occurrence of incident breast cancer
(which will or will not lead to death), respectively, as primary endpoints.
RESULTS: A total of 18 BC specific DNAme patterns were discovered in tissue, of which the top six were further tested in
serum. The best candidate, EFC#93, was validated for clinical use. EFC#93 was an independent poor prognostic marker in
pre-chemotherapy samples (hazard ratio [HR] for death = 7.689) and superior to circulating tumor cells (CTCs)
(HR for death = 5.681). More than 70% of patients with both CTCs and EFC#93 serum DNAme positivity in
their pre-chemotherapy samples relapsed within five years. EFC#93-positive disseminated disease in post-chemotherapy
samples seems to respond to anti-hormonal treatment. The presence of EFC#93 serum DNAme identified 42.9% and 25%
of women who were diagnosed with a fatal BC within 3–6 and 6–12 months of sample donation, respectively, with a
specificity of 88%. The sensitivity with respect to detecting fatal BC was ~ 4-fold higher compared to non-fatal BC.
CONCLUSIONS: Detection of EFC#93 serum DNAme patterns offers a new tool for early diagnosis and management of
disseminated breast cancers. Clinical trials are required to assess whether EFC#93-positive women in the absence of
radiological detectable breast cancers will benefit from anti-hormonal treatment before the breast lesions become
clinically apparent
The Influence of the effect of solute on the thermodynamic driving force on grain refinement of Al alloys
Grain refinement is known to be strongly affected by the solute in cast alloys. Addition of some solute can reduce grain size considerably while others have a limited effect. This is usually attributed to the constitutional supercooling which is quantified by the growth restriction factor, Q. However, one factor that has not been considered is whether different solutes have differing effects on the thermodynamic driving force for solidification. This paper reveals that addition of solute reduces the driving force for solidification for a given undercooling, and that for a particular Q value, it is reduced more substantially when adding eutectic-forming solutes than peritectic-forming elements. Therefore, compared with the eutectic-forming solutes, addition of peritectic-forming solutes into Al alloys not only possesses a higher initial nucleation rate resulted from the larger thermodynamic driving force for solidification, but also promotes nucleation within the constitutionally supercooled zone during growth. As subsequent nucleation can occur at smaller constitutional supercoolings for peritectic-forming elements, a smaller grain size is thus produced. The very small constitutional supercooling required to trigger subsequent nucleation in alloys containing Ti is considered as a major contributor to its extraordinary grain refining efficiency in cast Al alloys even without the deliberate addition of inoculants.The Australian Research Council (ARC DP10955737)
Quality of life and metabolic status in mildly depressed women with type 2 diabetes treated with paroxetine: A single-blind randomised placebo controlled trial
BACKGROUND: Depression is prevalent in people with type 2 diabetes and affects both glycemic control and overall quality of life. The aim of this trial was to evaluate the effect of the antidepressant paroxetine on metabolic control, quality of life and mental well-being in mildly depressed women with type 2 diabetes. METHODS: We randomised 15 mildly depressed women with non-optimally controlled type 2 diabetes to a 10-week single-blind treatment with either paroxetine 20 mg per day or placebo. Primary efficacy measurements were glycemic control and quality of life. Glycosylated hemoglobin A(1c )(GHbA(1c)) was used as a measure of glycemic control. Quality of life was evaluated using RAND-36. Mental state was assessed using two clinician-rated scoring instruments, Hamilton's Anxiety Scale (HAM-A) and Montgomery-Åsberg's Depression Rating Scale (MADRS), and a patient-rated scoring instrument, Beck's Depression Inventory (BDI). RESULTS: At the end of the study no significant difference between groups in improvement of quality of life was found. A trend towards a superior improvement in glycemic control was found in the paroxetine group (p = 0.08). A superior increase in sex-hormone-binding-globuline (SHBG) levels was evidenced in the paroxetine group (p = 0.01) as a sign of improved insulin sensitivity. There was also a trend for superior efficacy of paroxetine in investigator-rated anxiety and depression. This notion was supported by a trend for superior decrease of serum cortisol levels in the paroxetine group (p = 0.06). CONCLUSION: Paroxetine has a beneficial effect on measures of insulin sensitivity and may improve glycemic control. Larger studies of longer duration are needed to verify the benefits of paroxetine in type 2 diabetes. While waiting for more conclusive evidence it seems sensible to augment standard care of type 2 diabetes with paroxetine even in patients who do not fulfil routine psychiatric criteria for initiation of antidepressant drug treatment
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