2019 - First Black Male Associate Dean, Dexter Smith

Photograph of Dexter Smith. The appointment of Smith as Associate Dean of Admissions marks the first time a Black man holds the title of Associate Dean at William & Mary Law School.https://scholarship.law.wm.edu/blackhistorywmls/1024/thumbnail.jp

The Industrial Evolution of the United States

A thesis which describes the evolution of industry in the United States, chronicling from 1789 to the following one hundred years

Please God, make room for a Little Boy!

https://digitalcommons.library.umaine.edu/mmb-vp/4490/thumbnail.jp

Pathological histone acetylation in Parkinson's disease: Neuroprotection and inhibition of microglial activation through SIRT 2 inhibition

Parkinson's disease (PD) is associated with degeneration of nigrostriatal neurons due to intracytoplasmic inclusions composed predominantly of a synaptic protein called α-synuclein. Accumulations of α-synuclein are thought to 'mask' acetylation sites on histone proteins, inhibiting the action of histone acetyltransferase (HAT) enzymes in their equilibrium with histone deacetylases (HDACs), thus deregulating the dynamic control of gene transcription. It is therefore hypothesised that the misbalance in the actions of HATs/HDACs in neurodegeneration can be rectified with the use of HDAC inhibitors, limiting the deregulation of transcription and aiding neuronal homeostasis and neuroprotection in disorders such as PD. Here we quantify histone acetylation in the Substantia Nigra pars compacta (SNpc) in the brains of control, early and late stage PD cases to determine if histone acetylation is a function of disease progression. PD development is associated with Braak-dependent increases in histone acetylation. Concurrently, we show that as expected disease progression is associated with reduced markers of dopaminergic neurons and increased markers of activated microglia. We go on to demonstrate that in vitro, degenerating dopaminergic neurons exhibit histone hypoacetylation whereas activated microglia exhibit histone hyperacetylation. This suggests that the disease-dependent increase in histone acetylation observed in human PD cases is likely a combination of the contributions of both degenerating dopaminergic neurons and infiltrating activated microglia. The HDAC SIRT 2 has become increasingly implicated as a novel target for mediation of neuroprotection in PD: the neuronal and microglial specific effects of its inhibition however remain unclear. We demonstrate that SIRT 2 expression in the SNpc of PD brains remains relatively unchanged from controls and that SIRT 2 inhibition, via AGK2 treatment of neuronal and microglial cultures, results in neuroprotection of dopaminergic neurons and reduced activation of microglial cells. Taken together, here we demonstrate that histone acetylation is disease-dependently altered in PD, likely due the effects of dopaminergic neurodegeneration and microglial infiltration; yet SIRT 2 remains relatively unaltered with disease. Given the stable nature of SIRT 2 expression with disease and the effects of SIRT 2 inhibitor treatment on degenerating dopaminergic neurons and activated microglia detected in vitro, SIRT 2 inhibitors warrant further investigation as potential therapeutics for the treatment of the PD

Elite interviewing in professional organizations

Interviewing elites presents distinctive methodological challenges, which are exacerbated when interviewing elite professionals. These individuals (i.e. senior professionals and professionals in elite professional organizations) are typically relatively powerful, highly educated, and self-assured, and work in organizations which guard their external image very carefully. Over the past 25 years I have interviewed many hundreds of senior professionals in elite professional organizations. For this article, I have reflected on my experiences and have asked senior professionals to reflect on their own experience of research interviews. Bringing together insights of both interviewees and interviewers, this article provides an opportunity for researchers to reflect upon and improve their professional practice when conducting elite interviews

Hark! Hark! Hark!

We were thinking of home, yes! Of dear ones at home, When faint came the tap of the drum, And we listened again, for we hoped to be free, We hoped that our brave boys had come; There were tears in our eyes, as the drum beat once more, Our hearts seemed to thrill with sweetest joy, For the flag was in sight that would banish our pain, Restore to the mother her boy! CHORUS Hark! Hark! Hark! We hear them coming! Loved one, we’ll soon be home with thee! Oh! Ring the bells! Boom the guns! Shout hurrah! ‘Tis over, and all now are free! Hark! Hark! Hark! We hear them coming! Loved one, we’ll soon be home with thee! Hark! Hark! Hark! We hear them coming! Loved one, we’ll soon be home with thee! Hark! Hark! Hark! We hear them coming! Loved one, we’ll soon be home with thee! Oh! Ring the bells! Boom the guns! Shout hurrah! ‘Tis over, and all now are free! Oh! Ring the bells! Boom the guns! Shout hurrah! ‘Tis over, and all now are free! Oh! Ring the bells! Boom the guns! Shout hurrah! ‘Tis over, and all now are free! We had dreamed of the time when the war should be o’er, We felt that sweet peace hovered near, And we shouted as mortals ne’er shouted before, And gave the brave boys cheer on cheer! We’ll remember the boys who have opened the doors And said to the prisoner “go free!” That he might see the Union triumphant again And Freedom from sea to the sea

The Origin of UV-optical Variability in AGN and Test of Disc Models: XMM-Newton and ground based observations of NGC4395

The origin of short timescale (weeks/months) variability of AGN, whether due to intrinsic disc variations or reprocessing of X-ray emission by a surrounding accretion disc, has been a puzzle for many years. However recently a number of observational programmes, particularly of NGC5548 with Swift, have shown that the UV/optical variations lag behind the X-ray variations in a manner strongly supportive of X-ray reprocessing. Somewhat surprisingly the implied size of the accretion disc is ~3x greater than expected from a standard, smooth, Shakura-Sunyaev thin disc model. Although the difference may be explained by a clumpy accretion disc, it is not clear whether the difference will occur in all AGN or whether it may change as, eg, a function of black hole mass, accretion rate or disc temperature. Measurements of interband lags for most AGN require long timescale monitoring, which is hard to arrange. However for low mass (<1 million solar mass) AGN, the combination of XMM-Newton EPIC (X-rays) with the optical monitor in fast readout mode allows an X-ray/UV-optical lag to be measured within a single long observation. Here we summarise previous related observations and report on XMM-Newton observations of NGC4395 (mass ~100x lower and accretion rate ~20x lower than for NGC5548). We find that the UVW1 lags the X-rays by ~470s. Simultaneous observations at 6 different ground based observatories also allowed the g-band lag (~800s) to be measured. These observations are in agreement with X-ray reprocessing but initial analysis suggests that, for NGC4395, they do not differ markedly from the predictions of the standard thin disc model.Comment: 6 pages, 16 figures, accepted for publication in Astronomische Nachrichte

Math Description Engine Software Development Kit

The Math Description Engine Software Development Kit (MDE SDK) can be used by software developers to make computer-rendered graphs more accessible to blind and visually-impaired users. The MDE SDK generates alternative graph descriptions in two forms: textual descriptions and non-verbal sound renderings, or sonification. It also enables display of an animated trace of a graph sonification on a visual graph component, with color and line-thickness options for users having low vision or color-related impairments. A set of accessible graphical user interface widgets is provided for operation by end users and for control of accessible graph displays. Version 1.0 of the MDE SDK generates text descriptions for 2D graphs commonly seen in math and science curriculum (and practice). The mathematically rich text descriptions can also serve as a virtual math and science assistant for blind and sighted users, making graphs more accessible for everyone. The MDE SDK has a simple application programming interface (API) that makes it easy for programmers and Web-site developers to make graphs accessible with just a few lines of code. The source code is written in Java for cross-platform compatibility and to take advantage of Java s built-in support for building accessible software application interfaces. Compiled-library and NASA Open Source versions are available with API documentation and Programmer s Guide at http:/ / prim e.jsc.n asa. gov

Put Me In My Little Bed

[Verse 1] Oh! birdie, I am tired now, I do not care to hear you sing; You’ve sung your happy songs all day, Now put your head beneath your wing; I’m sleepy too as I can be, And sister, when my pray’r is said, I want to lay me down to rest, So put me in my little bed. [Chorus] Come, sister, come, Kiss me good night, For I my evening pray’r have said; I’m tired now and sleepy too, Come , put me in my little bed. [Verse 2] Oh! sister, what did mother say, When she was call’d to Heav’n away? She told me always to be good, And never, never go stray; I can’t forget the day she died, She placed her hand upon my head, She whisper’d softly, “keep my child,” And then they told me she was dead. [Chorus] [Verse 3] Dear sister, come and hear my pray’r, Now ere I lay me down to sleep, Within my Heav’nly Father’s care, While angels bright their vigils keep; And let me ask of Him above, To keep my soul in paths of right, Oh! let me thank Him for His love,Ere I shall say my last “good night.” [Chorus

Genetic susceptibility, elevated blood pressure and risk of atrial fibrillation:A Mendelian randomization study

Background: Whether elevated blood pressure (BP) is a modifiable risk factor for atrial fibrillation (AF) is not established. We tested (1) whether the association between BP and risk of AF is causal, (2) whether it varies according to individual&#x2019;s genetic susceptibility for AF, and (3) the extent to which specific BP-lowering drugs are expected to reduce this risk. Methods: First, causality of association was assessed through two-sample Mendelian randomization, using data from two independent genome-wide association studies that included a total of one million European population. Second, the UK Biobank data of 329,237 participants at baseline was used to study the effect of BP on AF according to genetic susceptibility of developing AF. Third, a possible treatment effect with major BP-lowering drug classes on AF risk was predicted through genetic variants in genes encode the therapeutic targets of each drug class. Estimated drug effects were compared with effects on incident coronary heart disease, for which direct trial evidence exists. Results: The two-sample Mendelian randomization analysis indicated that, on average, exposure to a higher systolic BP increased the risk of AF by 19% (odds ratio per each 10-mm Hg [OR]: 1.19 [1.12 to 1.27]). This association was replicated in the UK biobank using individual participant data. However, in a further genetic risk-stratified analysis, there was evidence for a linear gradient in the relative effects of systolic BP on AF; while there was no conclusive evidence of an effect in those with low genetic risk, a strong effect was observed among those with high genetic susceptibility for AF. The comparison of predicted treatment effects using genetic proxies for three main drug classes (angiotensin-converting enzyme inhibitors, beta-blockers and calcium channel blockers) suggested similar average effects for the prevention of atrial fibrillation and coronary heart disease. Conclusions: The effect of elevated BP on the risk of AF is likely to be causal, suggesting that BP-lowering treatment may be effective in AF prevention. However, average effects masked clinically important variations, with a more pronounced effect in individuals with high genetic susceptibility risk for AF