Cuando los Negros Luchaban (the Black Struggle): 1965 U.S. invasion of the Dominican Republic [abstract]

Abstract only availableOn April 22, 1965, in Santo Domingo, the Dominican Republic, left winged military men launched a coup against the U.S. backed president in order to restore the presidency of Juan Bosch, a proclaimed populist whom the United States had helped oust from power only months before. The backlash of the April coup involved the invasion of 14,000 U.S. troops into the Dominican Republic. In the eyes of the U.S. Department of State, the Dominican Republic, whose population contains ninety percent of individuals of African heritage, would not become another Cuba. In the United States, the stage of 1965 is set with contentious involvement in the Vietnam war, a large-scale civil rights movement steadily rolling along and gaining momentum and headed by African Americans, and a host of fearful and zealous Latin American foreign policies. Observing this scene, this paper raises the questions: How did black Americans respond to the United States' use of force towards their presumed “brothers” to the south? Did ideology override race in the international relations between blacks of the African Diaspora? Are the bonds of the African Diaspora as strong as intellectuals have historically suggested and advocated? Or are these bonds products of myth and merely tools for empowerment? Are they simply broken and in need of repair? Are there valid arguments for unity between members of the African Diaspora? In response to these inquiries, the paper places obstacles before the perpetuators of modern-day “racial” classifications, cultural perspectives, and political assumptions, in preparation to renew the discourse surrounding blacks of the world

A target repurposing approach identifies N-myristoyltransferase as a new candidate drug target in filarial nematodes

Myristoylation is a lipid modification involving the addition of a 14-carbon unsaturated fatty acid, myristic acid, to the N-terminal glycine of a subset of proteins, a modification that promotes their binding to cell membranes for varied biological functions. The process is catalyzed by myristoyl-CoA:protein N-myristoyltransferase (NMT), an enzyme which has been validated as a drug target in human cancers, and for infectious diseases caused by fungi, viruses and protozoan parasites. We purified Caenorhabditis elegans and Brugia malayi NMTs as active recombinant proteins and carried out kinetic analyses with their essential fatty acid donor, myristoyl-CoA and peptide substrates. Biochemical and structural analyses both revealed that the nematode enzymes are canonical NMTs, sharing a high degree of conservation with protozoan NMT enzymes. Inhibitory compounds that target NMT in protozoan species inhibited the nematode NMTs with IC50 values of 2.5-10 nM, and were active against B. malayi microfilariae and adult worms at 12.5 µM and 50 µM respectively, and C. elegans (25 µM) in culture. RNA interference and gene deletion in C. elegans further showed that NMT is essential for nematode viability. The effects observed are likely due to disruption of the function of several downstream target proteins. Potential substrates of NMT in B. malayi are predicted using bioinformatic analysis. Our genetic and chemical studies highlight the importance of myristoylation in the synthesis of functional proteins in nematodes and have shown for the first time that NMT is required for viability in parasitic nematodes. These results suggest that targeting NMT could be a valid approach for the development of chemotherapeutic agents against nematode diseases including filariasis

Membrane mediated motor kinetics in microtubule gliding assays.

Motor-based transport mechanisms are critical for a wide range of eukaryotic cell functions, including the transport of vesicle cargos over long distances. Our understanding of the factors that control and regulate motors when bound to a lipid substrate is however incomplete. We used microtubule gliding assays on a lipid bilayer substrate to investigate the role of membrane diffusion in kinesin-1 on/off binding kinetics and thereby transport velocity. Fluorescence imaging experiments demonstrate motor clustering on single microtubules due to membrane diffusion in the absence of ATP, followed by rapid ATP-induced dissociation during gliding. Our experimental data combined with analytical modeling show that the on/off binding kinetics of the motors are impacted by diffusion and, as a consequence, both the effective binding and unbinding rates for motors are much lower than the expected bare rates. Our results suggest that motor diffusion in the membrane can play a significant role in transport by impacting motor kinetics and can therefore function as a regulator of intracellular transport dynamics

Toward Early-Warning Detection of Gravitational Waves from Compact Binary Coalescence

Rapid detection of compact binary coalescence (CBC) with a network of advanced gravitational-wave detectors will offer a unique opportunity for multi-messenger astronomy. Prompt detection alerts for the astronomical community might make it possible to observe the onset of electromagnetic emission from (CBC). We demonstrate a computationally practical filtering strategy that could produce early-warning triggers before gravitational radiation from the final merger has arrived at the detectors.Comment: 16 pages, 7 figures, published in ApJ. Reformatted preprint with emulateap

The Effects of Ultra-Long-Range Flights on the Alertness and Performance of Aviators

This investigation assessed the impact of ultra-long-range (ULR) simulator flights, departing either in the morning or late evening, on the alertness and performance of 17 commercial aviators. Immediately prior to and throughout each flight, alertness and performance were assessed via a computerized test of sustained attention, subjective questionnaires, and "hand-flying" tasks. There were fatigue-related effects on the majority of assessments, and the nature of these effects was consistent across the vigilance and self-report measures. However, the operational "hand-flying" manuevers proved insensitive to the impact of fatigue probably due to procedural factors. Regardless, the results of the present study suggest that fatigue associated with prolonged wakefulness in ULR flight operations will interact with flight schedules due to circadian and homeostatic influences. In this study, the pilots departing at night were at a greater initial disadvantage (during cruise) than pilots who departed earlier in the day; whereas those who departed earlier tended to be most impaired towards the end of the flight prior to landing. In real-world operations, airlines should consider the ramifications of flight schedules and what is known about human sleep and circadian rhythms to optimize safety

Air, ground, and groundwater recharge temperatures in an alpine setting, Brighton Basin, Utah

pre-printNoble gases are useful tracers for constraining groundwater recharge temperature and elevation, critical in determining source areas of groundwater recharge in mountainous terrain. A monitoring network in the alpine Brighton Basin in the Wasatch Mountains of northern Utah, USA, was established to examine the relationship between air temperatures, ground temperatures, and noble gas groundwater recharge temperatures. Maximum noble gas groundwater recharge temperatures computed using the closed-system equilibration model from 25 samples collected over the 2 year period 2007 to 2009 averaged 2.9 6 1.2°C, within the experimental error of the mean ground temperature of 2.3°C measured within the probable recharge area. Maximum noble gas recharge temperatures vary from 0 to 7°C, also comparable to ground temperature variations in the region. Groundwater ages in the collected samples vary from 0 to 7 years indicating changing flow paths to the collection site during the experiment. Mean ground temperatures in the upper 1 m of soil over the 2 year time period is 2.3°C, which is 1°C cooler than the mean surface air temperature extrapolated from a nearby meteorological station. This comparison contradicts an earlier observation that mean annual ground temperatures in central Utah are generally warmer than air temperatures. The offset in the Brighton Basin is explained by modeling a snow effect on ground temperature. This detailed study suggests that interpretation of groundwater recharge temperatures derived from noble gases should be attentive to the complex local ground temperature effects in the recharge areas

Engineers’ perceptions of the importance of empathy and care: initial insights from engineers practicing in Australia

Empathy and care influence aspects of engineering practice including collaboration and teamwork, stakeholder engagement, and quality of work. Empathy has been identified as a key employability skill for professionals, and is the foundation for many skills and attributes anticipated as required by future engineers. Therefore, the understanding of empathy and care, and consideration of the development of empathetic and caring competencies are increasingly relevant for engineering education. Recent studies have explored the conceptualisation of and value placed on empathy and care in engineering practice, from the perspectives of practicing engineers in US and German contexts. We broaden this to include the Australian setting. Engineers’ perceptions of empathy and care within Australian engineering practice were collected using an online version of the Empathy and Care Questionnaire (ECQ) instrument developed by Hess, Strobel, Pan and Wachter Morris (N = 183). Statistical analysis of survey questions relating to the perceived importance and benefits of empathy and care to engineers, and relevance within a range of engineering practice situations was undertaken. Analysis of gender, years of experience, and organisational role indicated that female engineers perceived empathy and care to be more important, and more impactful on engineering practice than male engineers. Perceptions of empathy and care did not vary with duration of engineering work experience, however engineers in positions of organisational leadership placed greater importance on empathy and care in their roles than others. These differences contrast with results of the US and German studies. Further analysis is required to understand where, when and why these differences occur

Bridging adaptive management and reinforcement learning for more robust decisions

From out-competing grandmasters in chess to informing high-stakes healthcare decisions, emerging methods from artificial intelligence are increasingly capable of making complex and strategic decisions in diverse, high-dimensional, and uncertain situations. But can these methods help us devise robust strategies for managing environmental systems under great uncertainty? Here we explore how reinforcement learning, a subfield of artificial intelligence, approaches decision problems through a lens similar to adaptive environmental management: learning through experience to gradually improve decisions with updated knowledge. We review where reinforcement learning (RL) holds promise for improving evidence-informed adaptive management decisions even when classical optimization methods are intractable. For example, model-free deep RL might help identify quantitative decision strategies even when models are nonidentifiable. Finally, we discuss technical and social issues that arise when applying reinforcement learning to adaptive management problems in the environmental domain. Our synthesis suggests that environmental management and computer science can learn from one another about the practices, promises, and perils of experience-based decision-making.Comment: In press at Philosophical Transactions of the Royal Society

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al