152 research outputs found

    Emperipolesis in a Case of Adult T Cell Lymphoblastic Lymphoma (Mediastinal type)-Detected at FNAC and Imprint Cytology

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    Emperipolesis is a condition in which viable hematopoetic cells are seen intact in the cytoplasm of host cell without damage. This phenomenon is seen in many physiologic and pathologic conditions, its presence in Rosai Dorfman disease (RDD) is characteristic of the disease. However emperipolesis is an uncommon finding in malignant lymphoma both Hodgkins and non-Hodgkinā€™s lymphoma, wherein it has been described in bone marrow aspirate and tissue culture. In contrast there are only two case reports of emperipolesis phenomenon described in non-Hodgkinā€™s lymphoma in tissue sections. We report a case of an adult T cell lymphoblastic lymphoma (mediastinal type) with features of emperipolesis demonstrated at fine needle aspiration cytology (FNAC) and imprint cytology of cervical lymph nodes. To our knowledge, this is the first case report of emperipolesis in a case of adult T cell lymphoblastic lymphoma (mediastinal type)-detected at FNAC and imprint cytology

    Developing a labview based thermally stimulated current (tsc) controller to measure residual charge in electrospinning

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    Electrospinning is an electrohydrodynamic process for the fabrication of nanofibers which are widely used in therapeutical tissue engineering approaches. It utilizes the potential difference of an electrostatic field to overcome the surface tension of the polymer solution to extrude a fine jet of fluid which deposits on the grounded collector as a nanofiber mat. Using this process, nanofibers with diameters less than a micron can be produced. Previous studies have shown the presence of residual charge in electrospun nanofibers. The presence and decay of residual charge during cell culture media is still unknown. In an attempt to clarify the presence or absence of residual charge during cell culture, a LabVIEW based Thermally Stimulated Current controller is designed. The LabVIEW controller encapsulates the temperature and the electrometer control using RS- 485 and GPIB interfaces. The controller outputs a Temperature-Current plot which is the Thermally Stimulated Current spectrum. The current observed at the melting point of the electrospun material is a direct measure of the residual charge trapped within the nanofiber mat. Using this technique electrospun PolyCaproLactone (PCL) mats are analyzed before and after immersion in culture media and Phosphate Buffer Solution (PBS) for 1, 4 and 7 days

    Stochastic Processes as a Source of Cell to Cell Diversity and Cellular Ageing

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    Even populations of monoclonal cells exhibit phenotypic diversity. There are several sources generating such diversity, including stochasticity in the dynamics of gene expression, and the stochastic partitioning of molecules during division. This thesis focuses on the construction and simulation of a realistic model of gene expression and on the stochastic partitioning of cellular components during cell division. First, we present and make use of statistical methods to extract information on the kinetics of gene expression from live-cell measurements at the single RNA molecule level. This information allows us to characterize the kinetics of the multi-stepped process of transcription initiation, including the degree of noise in transcript production, as well as the kinetics of partitioning of protein aggregates by the cellā€™s poles. A model of single gene expression in a growing population of cells and a model of ageing in bacteria are then constructed based upon these measurements. Next, we present a new simulator which uses the Stochastic Simulation Algorithm to simulate the dynamics of intracellular processes in populations of cells, each of which able to grow and divide with random partitioning of molecules. Cells are represented in the simulator by compartments that can be created and destroyed at runtime. Logarithmic simulation algorithms and efficient data structures were designed and are here presented, which minimize the computational cost of simulating the dynamics of large cell populations that involve a large number of chemical reactions

    CFD Simulation of a Small Stirling Cryocooler Using Non-Thermal Equilibrium Model

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    Stirling Cryocoolers serve in a number of advanced technological applications to cool a variety of important components, such as infrared (IR) detectors, high temperature super conductors (HTSC), and cryogenic catheters. With the advancement in applications of cryocoolers, several simulations of such cryocoolers were also developed. These types of simulations can save a lot of time and money as it provide an accurate analysis of the performance of the cryocooler before actually manufacturing it. In this study, the commercial computational fluid dynamic (CFD) package Fluent and Gambit was utilized for modeling the entire Stirling cryocooler that includes a compressor, an after cooler, a transfer tube, a regenerator that is represented as porous medium and cold and warm heat exchangers. The regenerator is the key element of Stirling cycle cryocoolers. It can be seen that enactment of the regenerator straightly affects the cryocooler performance. Therefore, any improvement on the regenerator will lead to a more efficient cryocooler. This project represents completely new type of numerical computational fluid dynamic (CFD) approach for making it more realistic to the porous media inside the regenerator of a Stirling refrigerator. The available commercial software package FLUENT which is used for solving Computational fluid dynamics (CFD) has the capability to define a porous media and to solve the governing equation for this region

    Effects of Intracellular and Partitioning Asymmetries in Escherichia coli

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    Cell divisions in Escherichia coli are, in general, morphologically symmetric. However, in a few cases, significant asymmetries between sister cells exist. These asymmetries between sister cells result in functional differences between them. For example, cells inheriting the older pole, over generations, accumulate more unwanted protein aggregates than their sister and, consequently, have a reduced growth rate. The reduced ability of these cells to reproduce shows that even these unicellular organisms are susceptible to the effects of aging. To understand senescence in these organisms, it is critical to investigate the sources as well as the functional consequences of asymmetries in division.In this thesis, we characterize mechanisms responsible for functional and morphological asymmetries in division in E. coli cells, using live, single-cell, single-molecule imaging techniques and detailed stochastic models. First, to understand the functional asymmetries due to the heterogeneous spatial distribution of large, inert protein complexes, we study the kinetics of segregation and retention of such complexes by observing these events, one event at a time. For that, we track individual MS2-GFP tagged RNA complexes, as they move in the cell cytoplasm, and characterize the mechanisms responsible for their long-term spatial distribution and resulting partitioning. Next, to understand the morphological asymmetries, we study the difference in cell sizes between sister cells at division under different environmental conditions. Finally, we present the models and simulators developed to characterize and mimic these processes, as well as to explore their functional consequences.Our results suggest that functional and morphological asymmetries in division, in the growth conditions studied, appear to be mostly driven by the nucleoid. In particular, we find that the fluorescent complexes are retained at the poles due to nucleoid occlusion. Further, the positioning of the point of division is also regulated by the degree of proximity between the two replicated nucleoids in the cell at the moment preceding division. Finally, based on simulation results of the models in extreme conditions, we suggest that asymmetries in these processes in division can enhance the mean vitality of E. coli cell populations. Overall, the results suggest that nucleoid occlusion contributes, in different ways, to heterogeneities in E. coli cells that ultimately generate phenotypic differences between sister cells

    A normalized drug response metric improves accuracy and consistency of anticancer drug sensitivity quantification in cell-based screening

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    Accurate quantification of drug effects is crucial for identifying pharmaceutically actionable cancer vulnerabilities. Current cell viability-based measurements often lead to biased response estimates due to varying growth rates and experimental artifacts that explain part of the inconsistency in high-throughput screening results. We developed an improved drug scoring model, normalized drug response (NDR), which makes use of both positive and negative control conditions to account for differences in cell growth rates, and experimental noise to better characterize drug-induced effects. We demonstrate an improved consistency and accuracy of NDR compared to existing metrics in assessing drug responses of cancer cells in various culture models and experimental setups. Notably, NDR reliably captures both toxicity and viability responses, and differentiates a wider spectrum of drug behavior, including lethal, growth-inhibitory and growth-stimulatory modes, based on a single viability readout. The method will therefore substantially reduce the time and resources required in cell-based drug sensitivity screening. Abhishekh Gupta et al. present a normalized drug response (NDR) metric for accurate quantification of drug sensitivity in cell-based high-throughput assays. They show that NDR captures both toxicity and viability responses to improve drug effect classification over existing methods.Peer reviewe

    Influence of Neurotoxin Load on Parkinsonā€™s Disease Pathophysiology

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    Background: Parkinsonā€™s disease (PD) is a debilitating neurodegenerative disorder impacting movement, mood, and cognition. Among those affected, veterans, due to their occupational exposures, are particularly susceptible, contributing to over 110,000 PD cases in the United States. Studies have largely attributed this increased prevalence among veterans to environmental neurotoxins such as Agent Orange, MPTP, and 6-OHDA. However, it remains unclear how neurotoxin exposure load influences biological mechanisms in PD. This study aims to elucidate the influence of neurotoxin load on PD-associated molecular changes, neuroplasticity, neurodegeneration, and cognitive and motor function within a clinical population of the Rio Grande Valley region in Texas. Methods: Here we conducted a longitudinal, repeated-measures clinical observational study in PD patients with self-reported exposure to neurotoxins and sex-, age-, and occupation-matched healthy controls. Participants underwent comprehensive evaluations at two-time pointsā€”enrollment and 2 monthsā€”enabling the exploration of neurotoxin-related influences on disease progression. After enrollment, subjects underwent subjective surveys to assess prior neurotoxin exposure, including pesticides, Agent Orange, heavy metals, and other occupational or environmental toxins, and were evaluated for neurotoxins via blood samples. At all time points, we collected MRI and diffusion-weighted imaging (DWI) data to measure neurodegeneration, neurophysiological assessments using transcranial magnetic stimulation (TMS) to measure corticospinal excitability and neuroplasticity, and comprehensive functional evaluations encompassing motor function via MDS-UPDRS and HY scales, cognitive status via SLUMS, handedness via Edinburgh Handedness Inventory, gait analysis via Zenoā„¢ Walkway Gait Analysis System, and arm/hand functionality via Bionik InMotion2 Arm/Hand robot. Results and Discussion: To date, we have enrolled 7 participants with self-reported exposure to neurotoxins and 2 healthy controls. Enrolled PD subjects\u27 ages ranged from 66 to 87, with 5/7 reporting prior agricultural exposure to Pesticides (Methylbromide / Organochlorides) and 1 PD subject reporting exposure to engine exhaust from aviation fuel. One enrolled patient was withdrawn from the study due to an inability to obtain an MRI. Thus, we evaluated the 6 PD enrolled subjects. Initial motor UPDRS scoring revealed 4/6 patients with mild, 1/6 patients with moderate, and 1/6 patients with severe motor impairment of daily living. In addition, 5/6 patients exhibited mild and 1/6 patients revealed moderate impairment during motor examinations. Pending blood labs, the degree of influence neurotoxin blood has on motor and cognitive function remains to be seen. Data from prior PET studies have shown lower dopamine transporter uptake in all basal ganglia areas, as well as a higher asymmetry index in PD patients exposed to Agent Orange compared to PD patients with no exposure. In addition, PD symptoms have been shown to emerge more on the dominant hand side. Therefore, we expect increased cognitive and motor burden, especially on the dominant side, with increased neurotoxic load. Conclusion: This research holds considerable promise for advancing our understanding of PD, particularly in the context of neurotoxin-related etiology. By deciphering the molecular pathways influenced by neurotoxin exposure, the study sets the stage for targeted therapeutic interventions and potentially less invasive treatments, thereby improving the outlook for individuals grappling with neurotoxin-related PD

    Hiperurykemia wywołana stosowaniem diuretyku objawiająca się jako ostra dna moczanowa u 19-letniego chorego z umiarkowanym reumatycznym zwężeniem zastawki dwudzielnej

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    Gout, an inflammatory arthritis, is caused by an accumulation of monosodium urate crystals in the joints and soft tissues when serum uric acid concentrations rise above the physiological saturation limit (ā‰„ 6.4 mg/dL). Here, we report the case of a 19 year-old male who presented with gradually progressive, nontender swelling of multiple joints of the upper and lower limbs of eight monthsā€™ duration. He had been receiving frusemide 40 mg, spirinolactone 50 mg, metoprolol 50 mg, and erythromycin 250 mg twice daily for the previous 12 months on account of rheumatic mitral stenosis (moderate). Though a histological diagnosis of gout is the gold standard, in our case we diagnosed frusemide-induced secondary gout with malignant course. This was based on a combination of an imaging tool (radiology showing well defined, ā€˜punched-outā€™ erosions with overhanging edges), and clinical presentation (soft tissue nodules, i.e. tophi, calcification of tophi, and asymmetric involvement). Frusemide was stopped, allopurinol and other urate lowering agent were started which led to regression of his swelling.Zapalenie stawĆ³w w przebiegu dny moczanowej jest spowodowane akumulacją krysztaÅ‚Ć³w moczanu monosodowego w stawach i tkankach miękkich, gdy stężenie kwasu moczowego w surowicy wzrasta powyżej granicy nasycenia fizjologicznego (ā‰„ 6,4 mg/dl). W niniejszej pracy opisano przypadek 19-letniego mężczyzny, u ktĆ³rego przez ostatnie 8 miesięcy występował stopniowo postępujący, niebolesny obrzęk wielu stawĆ³w kończyn gĆ³rnej i dolnej. Przez ostatni rok chory stosował furosemid w dawce 40 mg, spironolakton w dawce 50 mg, metoprolol w dawce 50 mg i erytromycynę w dawce 250 mg 2 razy/dobę w ramach leczenia reumatycznego (umiarkowanego) zwężenia zastawki dwudzielnej. Choć ā€žzłotym standardemā€ w diagnostyce dny jest potwierdzenie rozpoznania w badaniu histologicznym, to w przedstawionym przypadku ā€” na podstawie połączenia danych z badań obrazowych (ostro obrysowane nadżerki z wystającymi krawędziami w badaniu radiologicznym) z obrazem klinicznym (guzki dnawe w tkankach miękkich [łac. tophi], zwapnienie i asymetryczne zajęcie stawĆ³w) ustalono, że furosemid wywołał wtĆ³rną dnę moczanową o złośliwym przebiegu. Po odstawieniu furosemidu i zastosowaniu allopurinolu i środka urykozurycznego obrzęki ustąpiły
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