Clear Writing for Public Administrators: A Refresher Workshop

Since you have been writing for years and since you have had many hours of classroom instruction in writing, you have a right to be skeptical about a writing workshop. What can be accomplished in a few hours that could not be accomplished in the preceding hundreds? That question has been the guiding principle behind this material. The most promising approach seemed to lie in comparing the work of professional writers with amateurs. To this end, the writing of a dozen public administrators was compared to the writing of authors published in such works as Harper\u27s, Smithsonian, INC, Nation\u27s Business, and Psychology Today

Remote sensing applications to resource problems in South Dakota

The author has identified the following significant results. Change in the vegetative structure was taking place in the Black Hills. Temporal analysis of the areal extent of open meadows was accomplished using black and white and color infrared aerial photography. A reduction of nearly 1100 hectares of open meadows was determined using photointerpretation. Techniques were developed for the management of meandering lakes, including use of LANDSAT imagery for continuous monitoring, classification of hydrophytes on low altitude CIR imagery, and planning and evaluation of improvements and multiple uses on aerial photography and photo mosaics. LANDSAT data were analyzed statistically from small and entire study scene areas to determine the effect of soils stratifications of corn signatures. Band 5 early season and band 7 later season recorded the strongest evidence of the influence of soils on corn signatures. Significant strata were determined by a multiple range test

CRISPLD1: a novel conserved target in the transition to human heart failure

Heart failure is a major health problem worldwide with a significant morbidity and mortality rate. Although studied extensively in animal models, data from patients at the compensated disease stage are lacking. We sampled myocardium biopsies from aortic stenosis patients with compensated hypertrophy and moderate heart failure and used transcriptomics to study the transition to failure. Sequencing and comparative analysis of analogous samples of mice with transverse aortic constriction identified 25 candidate genes with similar regulation in response to pressure overload, reflecting highly conserved molecular processes. The gene cysteine-rich secretory protein LCCL domain containing 1 (CRISPLD1) is upregulated in the transition to failure in human and mouse and its function is unknown. Homology to ion channel regulatory toxins suggests a role in Ca(2+) cycling. CRISPR/Cas9-mediated loss-of-function leads to dysregulated Ca(2+) handling in human-induced pluripotent stem cell-derived cardiomyocytes. The downregulation of prohypertrophic, proapoptotic and Ca(2+)-signaling pathways upon CRISPLD1-KO and its upregulation in the transition to failure implicates a contribution to adverse remodeling. These findings provide new pathophysiological data on Ca(2+) regulation in the transition to failure and novel candidate genes with promising potential for therapeutic interventions

Branding Dissent: Nitirat, Thailand’s Enlightened Jurists

This article examines the political role of a group of academic lawyers based at Thammasat University who have been seeking to reform various aspects of the Thai legal and judicial system. The seven-member group started out by criticising the illegality of the 2006 coup. After the 2010 crackdown against redshirt protestors, the group named itself Nitirat and started to hold seminars, draft legal proposals, and campaign to amend various laws. Nitirat has repeatedly challenged the legal and constitutional underpinnings of three key elements of the Thai state: the judiciary, the military, and the monarchy. In doing so, the group has gained a mass following, drawn mainly from those sympathetic to the “redshirt” movement which broadly supports former Prime Minister Thaksin Shinawatra. Informally led by scholar Worajet Pakeerat, Nitirat has created a popular branding which is reflected in huge audiences for public events, and the sales of souvenirs. The article aims to answer the following questions: How does Nitirat combine the roles of legal academic and political activist? How does it differ from the traditional mode of Thai public intellectuals? How significant is the Nitirat phenomenon

The functional consequences of sodium channel NaV 1.8 in human left ventricular hypertrophy

Aims In hypertrophy and heart failure, the proarrhythmic persistent Na+ current (I-NaL) is enhanced. We aimed to investigate the electrophysiological role of neuronal sodium channel Na(V)1.8 in human hypertrophied myocardium. Methods and results Myocardial tissue of 24 patients suffering from symptomatic severe aortic stenosis and concomitant significant afterload-induced hypertrophy with preserved ejection fraction was used and compared with 12 healthy controls. We performed quantitative real-time PCR and western blot and detected a significant up-regulation of Na(V)1.8 mRNA (2.34-fold) and protein expression (1.96-fold) in human hypertrophied myocardium compared with healthy hearts. Interestingly, Na(V)1.5 protein expression was significantly reduced in parallel (0.60-fold). Using whole-cell patch-clamp technique, we found that the prominent I-NaL was significantly reduced after addition of novel Na(V)1.8-specific blockers either A-803467 (30 nM) or PF-01247324 (1 mu M) in human hypertrophic cardiomyocytes. This clearly demonstrates the relevant contribution of Na(V)1.8 to this proarrhythmic current. We observed a significant action potential duration shortening and performed confocal microscopy, demonstrating a 50% decrease in proarrhythmic diastolic sarcoplasmic reticulum (SR)-Ca2+ leak and SR-Ca2+ spark frequency after exposure to both Na(V)1.8 inhibitors. Conclusions We show for the first time that the neuronal sodium channel Na(V)1.8 is up-regulated on mRNA and protein level in the human hypertrophied myocardium. Furthermore, inhibition of Na(V)1.8 reduced augmented I-NaL, abbreviated the action potential duration, and decreased the SR-Ca2+ leak. The findings of our study suggest that Na(V)1.8 could be a promising antiarrhythmic therapeutic target and merits further investigation

“A Good Personal Scientific Relationship”: Philip Morris Scientists and the Chulabhorn Research Institute, Bangkok

Jeff Collin and Ross MacKenzie analyze tobacco industry documents and find that Philip Morris consultants were able to gain access to a Thai research institute that is a WHO Collaborating Centre

Detrimental proarrhythmogenic interaction of Ca2+/calmodulin-dependent protein kinase II and NaV1.8 in heart failure

An interplay between Ca2+/calmodulin-dependent protein kinase IIδc (CaMKIIδc) and late Na+ current (INaL) is known to induce arrhythmias in the failing heart. Here, we elucidate the role of the sodium channel isoform NaV1.8 for CaMKIIδc-dependent proarrhythmia. In a CRISPR-Cas9-generated human iPSC-cardiomyocyte homozygous knock-out of NaV1.8, we demonstrate that NaV1.8 contributes to INaL formation. In addition, we reveal a direct interaction between NaV1.8 and CaMKIIδc in cardiomyocytes isolated from patients with heart failure (HF). Using specific blockers of NaV1.8 and CaMKIIδc, we show that NaV1.8-driven INaL is CaMKIIδc-dependent and that NaV1.8-inhibtion reduces diastolic SR-Ca2+ leak in human failing cardiomyocytes. Moreover, increased mortality of CaMKIIδc-overexpressing HF mice is reduced when a NaV1.8 knock-out is introduced. Cellular and in vivo experiments reveal reduced ventricular arrhythmias without changes in HF progression. Our work therefore identifies a proarrhythmic CaMKIIδc downstream target which may constitute a prognostic and antiarrhythmic strategy

Tachycardiomyopathy entails a dysfunctional pattern of interrelated mitochondrial functions

Tachycardiomyopathy is characterised by reversible left ventricular dysfunction, provoked by rapid ventricular rate. While the knowledge of mitochondria advanced in most cardiomyopathies, mitochondrial functions await elucidation in tachycardiomyopathy. Pacemakers were implanted in 61 rabbits. Tachypacing was performed with 330 bpm for 10 days (n = 11, early left ventricular dysfunction) or with up to 380 bpm over 30 days (n = 24, tachycardiomyopathy, TCM). In n = 26, pacemakers remained inactive (SHAM). Left ventricular tissue was subjected to respirometry, metabolomics and acetylomics. Results were assessed for translational relevance using a human-based model: induced pluripotent stem cell derived cardiomyocytes underwent field stimulation for 7 days (TACH–iPSC–CM). TCM animals showed systolic dysfunction compared to SHAM (fractional shortening 37.8 ± 1.0% vs. 21.9 ± 1.2%, SHAM vs. TCM, p < 0.0001). Histology revealed cardiomyocyte hypertrophy (cross-sectional area 393.2 ± 14.5 µm2 vs. 538.9 ± 23.8 µm2, p < 0.001) without fibrosis. Mitochondria were shifted to the intercalated discs and enlarged. Mitochondrial membrane potential remained stable in TCM. The metabolite profiles of ELVD and TCM were characterised by profound depletion of tricarboxylic acid cycle intermediates. Redox balance was shifted towards a more oxidised state (ratio of reduced to oxidised nicotinamide adenine dinucleotide 10.5 ± 2.1 vs. 4.0 ± 0.8, p < 0.01). The mitochondrial acetylome remained largely unchanged. Neither TCM nor TACH–iPSC–CM showed relevantly increased levels of reactive oxygen species. Oxidative phosphorylation capacity of TCM decreased modestly in skinned fibres (168.9 ± 11.2 vs. 124.6 ± 11.45 pmol·O2·s−1·mg−1 tissue, p < 0.05), but it did not in isolated mitochondria. The pattern of mitochondrial dysfunctions detected in two models of tachycardiomyopathy diverges from previously published characteristic signs of other heart failure aetiologies

Diglossia and identity in Northeast Thailand: Linguistic, social, and political hierarchy

The paper explores diglossic relations between Central Thai and phasa isan, a variety officially known as a dialect of Thai, but linguistically close to Lao. Phasa isan is spoken by almost one-third of Thailand's population but its speakers in the Northeast are often stigmatized as uneducated and backward. We conducted field research mainly among university students in Ubon Ratchathani, a northeastern border province, by drawing upon data from survey questionnaires, reflective essays, interviews, and field observations. The findings suggest a transitional diglossic relationship in which Central Thai is the High and phasa isan the Low variety. These relationships are discussed in terms of nationalism, social hierarchy, and language maintenance and shift