Juggling with light

We discovered that when a pair of small particles is optically levitated, the particles execute a dance whose motion resembles the orbits of balls being juggled. This motion lies in a plane perpendicular to the polarization of the incident light. We ascribe the dance to a mechanism by which the dominant force on each particle cyclically alternates between radiation pressure and gravity as each particle takes turns eclipsing the other. We explain the plane of motion by considering the anisotropic scattering of polarized light at a curved interface.Comment: 5 pages, 5 figures, 7 supplementary video

Explorations Into The Life Of Dictyostelium Discoideum.

In this dissertation, we explore several aspects of the Dictyostelium discoideum life cycle: growth, aggregation, and differentiation: We present experiments that question the conventional wisdom that vegetative D. discoideum are solitary individuals. We examine evidence - the cell density dependent transition from lag to exponential growth - which suggests that growth is stimulated by cell to cell interactions. Using a conditioned medium assay, we rule out the possibility that this interaction is through growth factors. Instead, we find that the interactions are short ranged. Next, we examine chemotactic, aggregation-stage cells. Using a microfluidic platform for cell stimulation, we investigate the timing of the biochemical signals involved in direction sensing, and we attempt to alter this timing. We flatten cells to various degrees and apply an external pulse of chemoattractant. The response is then monitored by imaging a fluorescent protein (PHCRAC -GFP or LimE-GFP) which translocates to the leading edge of the cell. We expect a dependence between the response time and the area of the cell, since the size should affect the time it takes for biochemical messengers to diffuse across the cell. The results were not definitive, because of the large variability in time it takes for the cell to respond to a signal. The large variability might be due to variations between the time the chemical signal is applied and the time it reaches the cell. To evaluate this possibility, we apply the theory of G.I. Taylor [172] and R. Aris [7] to answer the question of how quickly we are able to apply chemical signals to the target. We show that our platform for cell stimulation is the fastest available, and we rule out the pos- sibility that the variability in the response times is due to experimental setup. Rather, the source of variability must be biological, either intrinsic to each cell, or due to variability between cells (individuality). Recently, it was shown that D. discoideum cells are also capable of swimming chemotactically [13]. Using low Reynolds number flow simulations, we find evidence that supports the claim that the mechanisms employed by D. discoideum to swim are the same mechanisms employed when they crawl. Finally, we conclude our investigations by examining how D. discoideum sort out into regions of prestalk cells and prespore cells. Using a microfluidic flattening device with cells that express a fluorescent protein (CbpD::GFP) only if they are prestalk, we find indications that cell sorting is intrinsically a three dimensional process, as cell sorting was never observed in monolayer aggregates

Definition of valid proteomic biomarkers: a bayesian solution

Clinical proteomics is suffering from high hopes generated by reports on apparent biomarkers, most of which could not be later substantiated via validation. This has brought into focus the need for improved methods of finding a panel of clearly defined biomarkers. To examine this problem, urinary proteome data was collected from healthy adult males and females, and analysed to find biomarkers that differentiated between genders. We believe that models that incorporate sparsity in terms of variables are desirable for biomarker selection, as proteomics data typically contains a huge number of variables (peptides) and few samples making the selection process potentially unstable. This suggests the application of a two-level hierarchical Bayesian probit regression model for variable selection which assumes a prior that favours sparseness. The classification performance of this method is shown to improve that of the Probabilistic K-Nearest Neighbour model

Charge diffusion in the field-free region of charge-coupled devices

The potential well in back-illuminated charge-coupled devices (CCDs) does not reach all the way to the back surface. Hence, light that is absorbed in the field-free region generates electrons that can diffuse into neighboring pixels and thus decreases the spatial resolution of the sensor. We present data for the charge diffusion from a near point source by measuring the response of a back-illuminated CCD to light emitted from a submicron diameter glass fiber tip. The diffusion of electrons into neighboring pixels is analyzed for different wavelengths of light ranging from 430 to 780 nm. To find out how the charge spreading into other pixels depends on the location of the light spot; the fiber tip could be moved with a piezoelectric translation stage. The experimental data are compared to Monte Carlo simulations and an analytical model of electron diffusion in the field-free region. The presented analysis can be used to predict the charge diffusion in other back-illuminated sensors, and the experiment is universally applicable to measure any type of sensors

On the Complementarity of Higgs and Radion Searches at LHC

Models with 3-branes in extra dimensions typically imply the existence of a radion, phi that can mix with the Higgs, h, thereby modifying the Higgs properties and the prospects for its detectability at the LHC. The presence of the phi will extend the scope of the LHC searches. Detection of both the phi and the h might be possible. In this paper, we study the complementarity of the observation of gg -> h, with h -> gamma gamma or h -> ZZ -> 4 leptons, and gg -> phi -> ZZ -> 4 leptons at the LHC in the context of the Randall-Sundrum model. The potential for determining the nature of the detected scalar(s) at the LHC and at an e+e- linear collider is discussed, both separately and in combination.Comment: 11 pages, 5 figure

VprBP/DCAF1 Regulates the Degradation and Nonproteolytic Activation of the Cell Cycle Transcription Factor FoxM1

The oncogenic transcription factor FoxM1 plays a vital role in cell cycle progression, is activated in numerous human malignancies, and is linked to chromosome instability. We characterize here a cullin 4-based E3 ubiquitin ligase and its substrate receptor, VprBP/DCAF1 (CRL4VprBP), which we show regulate FoxM1 ubiquitylation and degradation. Paradoxically, we also found that the substrate receptor VprBP is a potent FoxM1 activator. VprBP depletion reduces expression of FoxM1 target genes and impairs mitotic entry, whereas ectopic VprBP expression strongly activates a FoxM1 transcriptional reporter. VprBP binding to CRL4 is reduced during mitosis, and our data suggest that VprBP activation of FoxM1 is ligase independent. This implies a nonproteolytic activation mechanism that is reminiscent of, yet distinct from, the ubiquitin-dependent transactivation of the oncoprotein Myc by other E3s. Significantly, VprBP protein levels were upregulated in high-grade serous ovarian patient tumors, where the FoxM1 signature is amplified. These data suggest that FoxM1 abundance and activity are controlled by VprBP and highlight the functional repurposing of E3 ligase substrate receptors independent of the ubiquitin system

Light-Powered Reactivation of Flagella and Contraction of Microtubule Networks: Toward Building an Artificial Cell

Artificial systems capable of self-sustained movement with self-sufficient energy are of high interest with respect to the development of many challenging applications, including medical treatments, but also technical applications. The bottom-up assembly of such systems in the context of synthetic biology is still a challenging task. In this work, we demonstrate the biocompatibility and efficiency of an artificial light-driven energy module and a motility functional unit by integrating light-switchable photosynthetic vesicles with demembranated flagella. The flagellar propulsion is coupled to the beating frequency, and dynamic ATP synthesis in response to illumination allows us to control beating frequency of flagella in a light-dependent manner. In addition, we verified the functionality of light-powered synthetic vesicles in in vitro motility assays by encapsulating microtubules assembled with force-generating kinesin-1 motors and the energy module to investigate the dynamics of a contractile filamentous network in cell-like compartments by optical stimulation. Integration of this photosynthetic system with various biological building blocks such as cytoskeletal filaments and molecular motors may contribute to the bottom-up synthesis of artificial cells that are able to undergo motor-driven morphological deformations and exhibit directional motion in a light-controllable fashion.R.A., V.N., E.B., I.G., and A.G. acknowledge support from the European Union’s Horizon 2020 research and innovation programme under grant agreement MAMI No. 766007. C.K., A.B., E.B., K.S., I.G., T.V.K., and A.G. thank MaxSynBio Consortium, which is jointly funded by the Federal Ministry of Education and Research of Germany and the Max Planck Societ

Seborrheic Keratosis of the Conjunctiva: A Case Report

Seborrheic keratosis is a benign epithelial neoplasia that occurs mainly in the skin of the eyelids and face. We describe a case of seborrheic keratosis of the conjunctiva confirmed by histopathology. A 72-year-old man presented with a recurrent conjunctival mass involving the nasal side of his right eye. Clinically, a diagnosis of conjunctival papilloma was made, and a mass excision was performed. The histopathological analysis evidenced a conjunctival-covering epithelium with papillomatous changes and irregular acanthosis, at the expense of a proliferation of basaloid cells. In addition, the lesion exhibited multiple pseudohorn cysts containing keratin. With the above findings, a diagnosis of conjunctival seborrheic keratosis was established. The occurrence of seborrheic keratosis on the conjunctiva is rare. In this case, seborrheic keratosis was confirmed by pathologic report despite its similar appearance with papilloma. Seborrheic keratosis should be considered in the differential diagnosis of conjunctival lesions

A rapid high-performance semi-automated tool to measure total kidney volume from MRI in autosomal dominant polycystic kidney disease.

OBJECTIVES: To develop a high-performance, rapid semi-automated method (Sheffield TKV Tool) for measuring total kidney volume (TKV) from magnetic resonance images (MRI) in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: TKV was initially measured in 61 patients with ADPKD using the Sheffield TKV Tool and its performance compared to manual segmentation and other published methods (ellipsoidal, mid-slice, MIROS). It was then validated using an external dataset of MRI scans from 65 patients with ADPKD. RESULTS: Sixty-one patients (mean age 45 ± 14 years, baseline eGFR 76 ± 32 ml/min/1.73 m2) with ADPKD had a wide range of TKV (258-3680 ml) measured manually. The Sheffield TKV Tool was highly accurate (mean volume error 0.5 ± 5.3% for right kidney, - 0.7 ± 5.5% for left kidney), reproducible (intra-operator variability - 0.2 ± 1.3%; inter-operator variability 1.1 ± 2.9%) and outperformed published methods. It took less than 6 min to execute and performed consistently with high accuracy in an external MRI dataset of T2-weighted sequences with TKV acquired using three different scanners and measured using a different segmentation methodology (mean volume error was 3.45 ± 3.96%, n = 65). CONCLUSIONS: The Sheffield TKV Tool is operator friendly, requiring minimal user interaction to rapidly, accurately and reproducibly measure TKV in this, the largest reported unselected European patient cohort with ADPKD. It is more accurate than estimating equations and its accuracy is maintained at larger kidney volumes than previously reported with other semi-automated methods. It is free to use, can run as an independent executable and will accelerate the application of TKV as a prognostic biomarker for ADPKD into clinical practice. KEY POINTS: • This new semi-automated method (Sheffield TKV Tool) to measure total kidney volume (TKV) will facilitate the routine clinical assessment of patients with ADPKD. • Measuring TKV manually is time consuming and laborious. • TKV is a prognostic indicator in ADPKD and the only imaging biomarker approved by the FDA and EMA

QT Prolongation and Life Threatening Ventricular Tachycardia in a Patient Injected With Intravenous Meperidine (Demerol®)

QT prolongation is a serious adverse drug effect, which is associated with an increased risk of Torsade de pointes and sudden death. Many drugs, including both cardiac and non-cardiac drugs, have been reported to cause prolongation of QT interval. Although meperidine has not been considered proarrhythmic, we present a unique case of a 16-year-old boy without an underlying cardiac disease, who developed polymorphic ventricular tachycardia, ventricular fibrillation and QT prolongation after an intravenous meperidine injection. He had no mutation in long QT syndrome genes (KCNQ1, KCNH2, and SCN5A), but single nucleotide polymorphisms were reported, including H558R in SCNA5A and K897T in KCNH2