John Hale letter acknowledging a request to speak at the Mercantile Library Association, September 14, 1845.

Hale writes that he has been so harrassed with business that he has had but little time to attend to any thing else, or even to think of aught beside. I have had to continue almost alone against the whole pack of profligate & venal newspaper Editors set upon me.https://digitalcommons.wofford.edu/littlejohnmss/1283/thumbnail.jp

Leadership, Ascendancy, and Gender

By the year 2000 women will constitute more than 50 percent of the workforce in the United States, yet their representation in top management and executive-level positions continues to hover in the single digits. This “glass ceiling,” which is conceptualized as limiting women's advancement into these roles, has been the subject of much debate and research over the last fifteen years. As both an equal rights and key competitive issue, the topic of women and leadership is gaining ever-increasing emphasis and momentum in American corporations. Although leadership skills have been advocated as a key human capital/person-centered variable leading to managerial ascendancy for women, the empirical research directly investigating this link is virtually non-existent. This longitudinal study proposed to measure the strength of this relationship using a matched sample of male and female managers. Eighty-five subjects, from the same U.S. based health-care products corporation, had previously participated in a multirater assessment process where seven different facets of their leadership skills were evaluated. Time two data were collected on four objective measures of ascendancy: percent change in salary, number of promotions (job moves) either offered or accepted, change in number of direct reports, and change in number of indirect reports. Multivariate analysis of covariance indicated that perceived leadership ability did lead to increased ascendancy, specifically in terms of percent salary change, for the female managers, but not for the males. Multiple regressions indicated that the female managers were not rewarded, necessarily, for gender congruent behavior in this organization, while male managers did appear to be rewarded more so on that particular dimension. Implications of these findings for female managers in the workplace were discussed

The Thermal Fluctuations of Red Blood Cells

In this thesis, we describe the development of a new technique for determination of the mechanical properties of the red blood cell membrane from measurement of its thermal fluctuations. Experimentally, the shape fluctuations of the equatorial contours of red blood cells are recorded using fast phase-contrast video microscopy, from which the Fourier fluctuation spectrum is obtained and analysed. The experimentally obtained fluctuation spectra are interpreted using a coarse grained particle dynamics simulation which models the thermal fluctuations of an elastic mesh endowed with bending and shear elasticity, and constant volume and surface area. We demonstrate that the simulation correctly describes the mean shape of the red cell as well as the membrane thermal fluctuations. Comparison between theory and experiment leads to physically sound values for the relevant membrane elastic moduli and helps distinguish between the contributions of the lipid bilayer and the membrane skeleton. We extend this technique to investigate the mechanical response of red blood cells to oxidative stress. We show that it is possible to discriminate between the actions of different oxidising agents from their distinctive effects on the membrane thermal fluctuation spectrum. This allows comparative measures of the membrane material properties to be extracted using an approximate analytical model thus discriminating between the effects of each oxidising agent on different structural components of the membrane. This technique was also applied to investigate the response of the red blood cell to oxidative stress under simulated hyperglycemic conditions characteristic for disease states such as diabetes. We established that the membrane elasticity of glycated cells deteriorate much fasted under administration of hydrogen peroxide, which may be related to the observed microvascular complications in diabetes, characterised by disproportionately high levels of reactive oxidative species. We demonstrate that metformin, one of the most widely prescribed anti-diabetic drugs, has an ameliorative effect on the membrane mechanical properties, which is probably due to its anti-glycating effects. The technique provides a reproducible means to assess the effects of reactive oxidative species on the red blood cell membrane mechanical properties and distinguish between effects on the protein membrane skeleton and the lipid bilayer. This makes the new method of potential value in monitoring the effects of drug induced changes hence assessing progress of treatment in terms of the antioxidant or anti-glycation properties of administered drugs in diabetes or other conditions characterised by high levels of oxidative stress

Effect of hydroperoxides on red blood cell membrane mechanical properties

Copyright © 2011 Biophysical SocietyWe investigate the effect of oxidative stress on red blood cell membrane mechanical properties in vitro using detailed analysis of the membrane thermal fluctuation spectrum. Two different oxidants, the cytosol-soluble hydrogen peroxide and the membrane-soluble cumene hydroperoxide, are used, and their effects on the membrane bending elastic modulus, surface tension, strength of confinement due to the membrane skeleton, and 2D shear elastic modulus are measured. We find that both oxidants alter significantly the membrane elastic properties, but their effects differ qualitatively and quantitatively. While hydrogen peroxide mainly affects the elasticity of the membrane protein skeleton (increasing the membrane shear modulus), cumene hydroperoxide has an impact on both membrane skeleton and lipid bilayer mechanical properties, as can be seen from the increased values of the shear and bending elastic moduli. The biologically important implication of these results is that the effects of oxidative stress on the biophysical properties, and hence the physiological functions, of the cell membrane depend on the nature of the oxidative agent. Thermal fluctuation spectroscopy provides a means of characterizing these different effects, potentially in a clinical milieu

Red blood cell thermal fluctuations: comparison between experiment and molecular dynamics simulations

Copyright © 2013 Royal Society of ChemistryWe outline a new method of analysis of thermal shape fluctuations of red blood cells, based on comparison between experiments and coarse-grained molecular dynamics simulations. The fluctuations of 2D equatorial contours of red blood cells are recorded experimentally using fast phase-contrast video microscopy, from which the fluctuation spectrum is calculated. The spectrum is compared to the corresponding contour fluctuation spectrum obtained from a finite-temperature particle-dynamics simulation, modelling a cell with bending and shear elasticity and conserved volume and surface area. We demonstrate that the simulation correctly describes the mean cell shape as well as the membrane thermal fluctuations, returning physically sound values for the relevant membrane elastic moduli

Measuring the Volatility of the Political agenda in Public Opinion and News Media

This is the final version. Available on open access from Oxford University Press via the DOI in this recordData Availability Statement: Replication data and documentation are available at: https://github.com/euagendas/POLVOLRecent election surprises, regime changes, and political shocks indicate that political agendas have become more fast-moving and volatile. The ability to measure the complex dynamics of agenda change and capture the nature and extent of volatility in political systems is therefore more crucial than ever before. This study proposes a definition and operationalization of volatility that combines insights from political science, communications, information theory, and computational techniques. The proposed measures of fractionalization and agenda change encompass the shifting salience of issues in the agenda as a whole and allow the study of agendas across different domains. We evaluate these metrics and compare them to other measures such as issue-level survival rates and the Pedersen Index, which uses public-opinion poll data to measure public agendas, as well as traditional media content to measure media agendas in the UK and Germany. We show how these measures complement existing approaches and could be employed in future agenda-setting research.Engineering and Physical Sciences Research Council (EPSRC)Volkswagen Foundatio

Alemtuzumab induction and tacrolimus monotherapy in pancreas transplantation: One- and two-year outcomes

BACKGROUND. Alemtuzumab (Campath-1H) induction with tacrolimus monotherapy has been shown to provide effective immunosuppression for kidney, liver, lung, and small bowel transplantation. This drug combination was evaluated in pancreas transplant recipients. METHODS. Sixty consecutive pancreas transplants (30 simultaneous pancreas-kidney, 20 pancreas after kidney, and 10 pancreas alone) were carried out under this protocol between July 2003 to January 2005. The mean follow-up was 22 months (range 17-33). RESULTS. One-year patient, pancreas, and kidney allograft survival were 95%, 93%, and 90%, respectively. With 22 months follow-up, patient, pancreas, and kidney survival were 94%, 89%, and 87%, respectively. The rejection rate was 30% (18/60), with four patients (7%) experiencing steroid-resistant rejection. Major infection occurred in three (5%) patients resulting in two (3.3%) deaths from disseminated histoplasmosis and a herpes virus infection. One patient with cryptococcal meningitis was successfully treated. Seven (11.7%) patients experienced cytomegalovirus infection, all of whom responded to treatment with ganciclovir. One (1.7%) case of polymorphic posttransplant lymphoproliferative disease was seen, which regressed with a temporary discontinuation of tacrolimus and high-dose ganciclovir. The mean serum creatinine of the 30 simultaneous pancreas-kidney transplants at one year posttransplant was 1.37±0.33 mg/ml. The preexisting creatinine in pancreas after kidney transplants was not adversely affected by this immunosuppressive protocol. CONCLUSION. A single dose of perioperative alemtuzumab followed by daily tacrolimus monotherapy provides effective immunosuppression for pancreas transplantation, but the optimal use of this drug combination is not yet clear. © 2006 Lippincott Williams & Wilkins, Inc

Know The Star, Know the Planet. IV. A Stellar Companion to the Host star of the Eccentric Exoplanet HD 8673b

HD 8673 hosts a massive exoplanet in a highly eccentric orbit (e=0.723). Based on two epochs of speckle interferometry a previous publication identified a candidate stellar companion. We observed HD 8673 multiple times with the 10 m Keck II telescope, the 5 m Hale telescope, the 3.63 m AEOS telescope and the 1.5m Palomar telescope in a variety of filters with the aim of confirming and characterizing the stellar companion. We did not detect the candidate companion, which we now conclude was a false detection, but we did detect a fainter companion. We collected astrometry and photometry of the companion on six epochs in a variety of filters. The measured differential photometry enabled us to determine that the companion is an early M dwarf with a mass estimate of 0.33-0.45 M?. The companion has a projected separation of 10 AU, which is one of the smallest projected separations of an exoplanet host binary system. Based on the limited astrometry collected, we are able to constrain the orbit of the stellar companion to a semi-major axis of 35{60 AU, an eccentricity ? 0.5 and an inclination of 75{85?. The stellar companion has likely strongly in uenced the orbit of the exoplanet and quite possibly explains its high eccentricity.Comment: Accepted to the Astronomical Journal, 6 Pages, 5 Figure

Know the Star, Know the Planet. III. A Stellar Companion to the Host Star of the Eccentric Exoplanet HD 8673b

HD 8673 hosts a massive exoplanet in a highly eccentric orbit (e = 0.723). Based on two epochs of speckle interferometry a previous publication identified a candidate stellar companion. We observed HD 8673 multiple times with the 10 m Keck II telescope, the 5 m Hale telescope, the 3.63 m Advanced Electro-Optical System telescope, and the 1.5 m Palomar telescope in a variety of filters with the aim of confirming and characterizing the stellar companion. We did not detect the candidate companion, which we now conclude was a false detection, but we did detect a fainter companion. We collected astrometry and photometry of the companion on six epochs in a variety of filters. The measured differential photometry enabled us to determine that the companion is an early M dwarf with a mass estimate of 0.33–0.45 M_☉. The companion has a projected separation of 10 AU, which is one of the smallest projected separations of an exoplanet host binary system. Based on the limited astrometry collected, we are able to constrain the orbit of the stellar companion to a semimajor axis of 35–60 AU, an eccentricity ≤0.5, and an inclination of 75°–85°. The stellar companion has likely strongly influenced the orbit of the exoplanet and quite possibly explains its high eccentricity

Structural basis for CRISPR RNA-guided DNA recognition by Cascade

The CRISPR (clustered regularly interspaced short palindromic repeats) immune system in prokaryotes uses small guide RNAs to neutralize invading viruses and plasmids. In Escherichia coli, immunity depends on a ribonucleoprotein complex called Cascade. Here we present the composition and low-resolution structure of Cascade and show how it recognizes double-stranded DNA (dsDNA) targets in a sequence-specific manner. Cascade is a 405-kDa complex comprising five functionally essential CRISPR-associated (Cas) proteins (CasA1B2C6D1E1) and a 61-nucleotide CRISPR RNA (crRNA) with 5′-hydroxyl and 2′,3′-cyclic phosphate termini. The crRNA guides Cascade to dsDNA target sequences by forming base pairs with the complementary DNA strand while displacing the noncomplementary strand to form an R-loop. Cascade recognizes target DNA without consuming ATP, which suggests that continuous invader DNA surveillance takes place without energy investment. The structure of Cascade shows an unusual seahorse shape that undergoes conformational changes when it binds target DNA.