Development of cancer biomarker assays from dna in various bodily fluids

Abstract DNA from cancer cells can enter surrounding fluid after apoptosis or necrosis. This DNA can be identified by sampling and sequencing the fluid looking for the mutations that gave rise to the cancer, referred to as a liquid biopsy. We have developed several liquid biopsies for the purpose of diagnosis and treatment selection through the use of targeted PCR and high throughput sequencing. We used the SafeSeqS methodology, a molecular barcoding technology previously developed in this lab, to further reduce sequencing errors to aid us in finding these rare mutations. We developed assays that identified genetic mutations from saliva, blood plasma, and pancreatic cysts. We investigating head and neck squamous cell carcinoma (HNSCC) from the oral cavity, oropharynx, hypopharynx, and larynx in 93 patients using a combination of saliva and plasma. We first identified either the E7 gene of HPV 16 or a primary mutation in the tumor and then tried to detect their presence in saliva and plasma. We collected saliva from every patient, while we only had plasma samples from 43 patients. We found that saliva performed best in oral cavity cancers detecting 100% of those patients, while plasma performed similarly across all sites detecting 87% of HNSCC patients. We detected mutations in 96% of patients when both saliva and plasma were available. Pancreatic cyst fluid was used to aid clinicians in the classification of pancreatic cysts. We created an 8 gene panel to look for mutations as well as additional tests for loss of heterozygosity and aneuploidy. We used DNA from fluid captured through endoscopic aspiration as well as from surgically resected cysts. When combined with the typical clinical features we were able to accurately predict which cysts needed surgery with a sensitivity and specificity of 89% and 69% respectively. Each of these projects began as an attempt to aid clinicians in dealing with these various diseases. Our results illustrate that liquid biopsies can be developed into an effective tool for the fight against cancer

The eclipsing post-common envelope binary CSS21055: a white dwarf with a probable brown-dwarf companion

We report photometric observations of the eclipsing close binary CSS21055 (SDSS J141126+200911) that strongly suggest that the companion to the carbon-oxygen white dwarf is a brown dwarf with a mass between 0.030 and 0.074 Msun. The measured orbital period is 121.73min and the totality of the eclipse lasts 125s. If confirmed, CSS21055 would be the first detached eclipsing WD+BD binary. Spectroscopy in the eclipse could provide information about the companion's evolutionary state and atmospheric structure.Comment: 6 pages, 5 figure

L-selectin mediated leukocyte tethering in shear flow is controlled by multiple contacts and cytoskeletal anchorage facilitating fast rebinding events

L-selectin mediated tethers result in leukocyte rolling only above a threshold in shear. Here we present biophysical modeling based on recently published data from flow chamber experiments (Dwir et al., J. Cell Biol. 163: 649-659, 2003) which supports the interpretation that L-selectin mediated tethers below the shear threshold correspond to single L-selectin carbohydrate bonds dissociating on the time scale of milliseconds, whereas L-selectin mediated tethers above the shear threshold are stabilized by multiple bonds and fast rebinding of broken bonds, resulting in tether lifetimes on the timescale of $10^{-1}$ seconds. Our calculations for cluster dissociation suggest that the single molecule rebinding rate is of the order of $10^4$ Hz. A similar estimate results if increased tether dissociation for tail-truncated L-selectin mutants above the shear threshold is modeled as diffusive escape of single receptors from the rebinding region due to increased mobility. Using computer simulations, we show that our model yields first order dissociation kinetics and exponential dependence of tether dissociation rates on shear stress. Our results suggest that multiple contacts, cytoskeletal anchorage of L-selectin and local rebinding of ligand play important roles in L-selectin tether stabilization and progression of tethers into persistent rolling on endothelial surfaces.Comment: 9 pages, Revtex, 4 Postscript figures include

Bulk spectral function sum rule in QCD-like theories with a holographic dual

We derive the sum rule for the spectral function of the stress-energy tensor in the bulk (uniform dilatation) channel in a general class of strongly coupled field theories. This class includes theories holographically dual to a theory of gravity coupled to a single scalar field, representing the operator of the scale anomaly. In the limit when the operator becomes marginal, the sum rule coincides with that in QCD. Using the holographic model, we verify explicitly the cancellation between large and small frequency contributions to the spectral integral required to satisfy the sum rule in such QCD-like theories.Comment: 16 pages, 2 figure

From lean production to Industrie 4.0: More autonomy for employees?

The article examines the relationship between lean production and Industrie 4.0 focusing on the question of autonomy in the work process. In contrast to the claim made by official Industrie 4.0 concepts that the autonomy of the employees would increase, we see in the current implementation projects a tendency towards greater standardization and control of work. This is in continuity with concepts of lean production, but neglects the participation-oriented elements of lean production such as teamwork and shop-floor-based improvement activities. Our argument is developed by analyzing practical examples from three relevant fields (digital assistance systems, data-based process management, modular assembly). The conclusions of this article also discuss the extent to which the concept of individual autonomy is suitable for the assessment of Industrie 4.0 concepts, given the high levels of interdependence already achieved in production processes

Conditions for Factorizable Output From a Beam splitter

A beam splitter is one of the most important devices in an optics laboratory because of its handiness and versatility; equivalent devices are found in various quantum systems to couple two subsystems or to interfere them. While it is normal that two independent input fields are superposed at the beam splitter to give correlated outputs, identical Gaussian states interfere there to produce totally independent output fields. We prove that Gaussian states with same the variance are the only states which bring about factorizable output fields.Comment: 6 pages, published in PR

Induction of apoptosis in human cancer cells by targeting mitochondria with gold nanoparticles

A major challenge in designing cancer therapies is the induction of cancer cell apoptosis, although activation of intrinsic apoptotic pathways by targeting gold nanoparticles to mitochondria is promising. We report an in vitro procedure targeting mitochondria with conjugated gold nanoparticles and investigating effects on apoptosis induction in the human breast cancer cell line Jimt-1. Gold nanoparticles were conjugated to a variant of turbo green fluorescent protein (mitoTGFP) harbouring an amino-terminal mitochondrial localization signal. Au nanoparticle conjugates were further complexed with cationic maltotriose-modified poly(propylene imine) third generation dendrimers. Fluorescence and transmission electron microscopy revealed that Au nanoparticle conjugates were directed to mitochondria upon transfection, causing partial rupture of the outer mitochondrial membrane, triggering cell death. The ability to target Au nanoparticles into mitochondria of breast cancer cells and induce apoptosis reveals an alternative application of Au nanoparticles in photothermal therapy of cancer

Разработка системы электропитания малого космического аппарата

Объектом исследования является системы электропитания малого космического аппарата. Целью ВКР является проектирование системы электропитания малого космического аппарата (МКА) для дистанционного зондирования Земли. В результате исследования определены: характеристики малых космических аппаратов; структура системы электроснабжения; проведен расчет элементов схем; рассмотрены производственная и экологическая безопасность проекта; рассчитаны затраты на проектирование.The object of study is the power supply system of a small spacecraft. The aim of the WRC is to design a power system for a small spacecraft (MCA) for remote sensing of the Earth. The study identified: characteristics of small spacecraft; power system structure; Calculation of circuit elements; considered industrial and environmental safety of the project; Design costs are calculated

Aharonov-Bohm cages in two-dimensional structures

We present an extreme localization mechanism induced by a magnetic field for tight-binding electrons in two-dimensional structures. This spectacular phenomenon is investigated for a large class of tilings (periodic, quasiperiodic, or random). We are led to introduce the Aharonov-Bohm cages defined as the set of sites eventually visited by a wavepacket that can, for particular values of the magnetic flux, be bounded. We finally discuss the quantum dynamics which exhibits an original pulsating behaviour.Comment: 4 pages Latex, 3 eps figures, 1 ps figur