Guadecitabine, in combination with Cyclophosphamide, promotes anti- cancer immunity in BALB/c mice bearing 4T1 mouse mammary carcinoma

Background: The extremely high mortality rate of patients diagnosed with triple negative breast cancer makes it one of the deadliest forms of cancer. Due to the heterogenous nature of tumors, complete clearance is not achieved and clonal selection occurs resulting in tumor cells evading the immune system. I aim to design a therapeutic intervention that is able to elicit an effective immune response against the tumor and instill immunological memory to eradicate primary and metastatic lesions. I hypothesize that the combination of Guad and Cyp will synergize and promote anticancer immunity via increased expression of neo-tumor antigens and depletion of MDSCs and T-regs. Methods: Guadecitabine (Guad), is a second-generation DNA methyltransferase inhibitor (DMNTi) that has been reported to increase antigenicity and deplete myeloid-derived suppressor cells (MDSC’s). Cyclophosphamide (Cyp) is a chemotherapy that has been shown to deplete regulatory T-cells (T-regs). Both MDSD’s and T-regs suppress antitumor immunity. BALB/c mice were challenged with 4T1 tumor cells subcutaneously in the mammary fat pad region. 4T1-bearing mice were administered low-dose Guad and Cyp for ten consecutive days. Tumor growth curves, tumor-infiltrating lymphocytes (TILs) were measured and MDSC’s and T- regs levels were assessed by flow cytometry. Results: Results from this experiment showed significant synergy between Guad and Cyp with both drugs reducing the tumor size over monotherapy. Conclusions: Further analysis of the data along with future experiments will elucidate if this synergy is driven by the depletion of MDSC’s and T-regs alone or the increase in tumor antigenicity inducing increased numbers of TILs.https://scholarscompass.vcu.edu/gradposters/1078/thumbnail.jp

Altitude Performance and Operational Characteristics of YJ71-A-7 Turbojet Engine

Altitude performance of a YJ71-A-7 turbojet engine, with afterburner inoperative, was determined in the NACA Lewis altitude wind tunnel over a wide range of flight conditions. Engine speed and exhaust-nozzle area were controlled independently during this investigation. The variation of corrected values of air flow, net thrust, and fuel flow with corrected engine speed was not defined by a single curve with changes in altitude at given flight Mach number. Changes in altitude had very little effect on minimum specific fuel consumption at altitudes up to 45,000 feet. There is one exhaust-nozzle schedule that is nearly optimum for all flight conditions. Performance calculated from pumping characteristics agreed with experimental values and can therefore be used to extend engine performance data

Performance of a turbojet engine with adjustable first-stage turbine stator and variable-area exhaust nozzle

The performance of a turbojet engine with a two-stage turbine, an adjustable first-stage turbine stator, and a variable-area exhaust nozzle was investigated at selected constant engine speeds and two simulated flight conditions. For the particular component characteristics of the engine investigated, little improvement in thrust levels of interest by use of an adjustable rather than an optimum fixed first-stage turbine stator

Quantum work statistics at strong reservoir coupling

Calculating the stochastic work done on a quantum system while strongly coupled to a reservoir is a formidable task, requiring the calculation of the full eigenspectrum of the combined system and reservoir. Here we show that this issue can be circumvented by using a polaron transformation that maps the system into a new frame where weak-coupling theory can be applied. It is shown that the work probability distribution is invariant under this transformation, allowing one to compute the full counting statistics of work at strong reservoir coupling. Crucially this polaron approach reproduces the Jarzynski fluctuation theorem, thus ensuring consistency with the laws of stochastic thermodynamics. We apply our formalism to a system driven across the Landau-Zener transition, where we identify clear signatures in the work distribution arising from a non-negligible coupling to the environment. Our results provide a new method for studying the stochastic thermodynamics of driven quantum systems beyond Markovian, weak-coupling regimes.Comment: 15 pages, 3 figures, comments welcom

Product Analytics Based On Demographic Democratization

Product analytics is a blend of computational methods with the express purpose of facilitating the multifaceted process of decision-making based on demographic and consumer preferences.  This complex subject is derived from consensus theory and includes structured analytics, categories, and the combination of evidence.  The methodology is applicable to a wide range of business, economic, social, political, and strategic decisions.  The paper describes a product allocation application to demonstrate the concepts

Classification of occupations for economically active: Factor analysis of Registration Sub-Districts (RSDs) in 1891

This paper discusses how census data for 1851-1911 can be used to classify the occupations of the economically active population within Registration Sub-Districts (RSDs) for England and Wales 1851-1911 using a factor analysis methodology applied to all occupations. This paper is a pilot for 1891 for all occupied population, and by gender

Does early surgery improve outcomes for periprosthetic fractures of the hip and knee? : A systematic review and meta-analysis

Open access via Springer Compact AgreementPeer reviewedPublisher PD

Multidisciplinary analysis of a mummified cranium claimed to be that of a medieval execution victim

This article presents a multidisciplinary analysis of a human skull with preserved soft tissue curated by a small museum in Boscastle, Cornwall, UK. The skull lacks a mandible and is coated in a black tar-like substance. Records left by a previous museum curator (now deceased) claimed the skull to be the head of a medieval execution victim. The skull was purportedly recovered from a London church that was destroyed during the Second World War where it had been kept in a carved oak box. If these details are correct, the skull would appear to have been venerated as a relic. The skull and box have been analysed using a range of techniques including computerised tomography, laser scanning, microscopy, infrared spectroscopy and radiocarbon dating. These analyses demonstrated the skull in fact to be that of an Egyptian mummy dating from the Ptolemaic period. Other instances have been noted of parts of Egyptian mummies being presented as European saintly relics, and the ‘Boscastle skull’ would appear to be an example of such. A wider point illustrated by the work presented here is that sufficient application of modern analytical techniques may reveal considerable information regarding human remains which otherwise have little or no provenance. This point strengthens arguments for the retention of such remains by curating institutions