EHD1 As a Positive Regulator of Macrophage Colony-Stimulating Factor-1 Receptor

The master regulator of the macrophage development, differentiation, proliferation, survival, phagocytosis, cytokine secretion, motility, adhesion, migration, and spreading is the receptor tyrosine kinase (RTK) colony stimulating factor-1 receptor (CSF-1R). Aberrant CSF-1R signaling is present amongst a variety of highly prevalent and devastating human diseases in the United States such as atherosclerosis, cancer, inflammatory bowel disease, arthritis, and neuro-demyelination/neuro-degeneration. A better understanding of basic mechanisms that govern macrophage development and function is of vital importance in treating patients afflicted with these conditions/diseases. CSF-1R presentation on the macrophage cell surface is a required precursor for CSF1- induced RTK dimerization (activation) and downstream CSF-1R signaling cascades. Mechanisms which regulate CSF-1R trafficking are unstudied and mechanisms of RTK trafficking regulation are poorly understood. The evolutionarily conserved C-terminal Eps15 Homology Domain (EHD) protein family consists of vesicular trafficking regulating proteins. However, the role of EHD proteins in CSF-1R trafficking and signaling has not been studied. I have utilized primary (non-immortalized) murine/mammalian macrophages under inducible Ehd1 gene deletion/knockout (EHD1-KO) to explore the role of EHD1 in CSF-1R trafficking in macrophages. I have discovered an entirely novel function for EHD1 in anterograde transport and presentation of CSF-1R on the macrophage cell surface. EHD1-KO macrophages have significantly depleted total and surface CSF-1R expression (i.e. receptor available for ligand-binding and subsequently CSF-1R activation/signaling) when compared with control macrophages. In EHD1-KO macrophages, newly synthesized CSF-1R en route to the cell surface is essentially shunted to the lysosome and degraded. These findings reveal an entirely novel and essential role for EHD1 in anterograde transport/presentation of CSF-1R to the macrophage cell surface

Sub micron area Nb/AlO(x)/Nb tunnel junctions for submillimeter mixer applications

In this paper, we report on a fabrication process developed for submicron area tunnel junctions. We have fabricated Nb/AlO(x)/Nb tunnel junctions with areas down to 0.1 sq micron using these techniques. The devices have shown excellent performance in receiver systems up to 500 GHz and are currently in use in radio astronomy observatories at 115, 230, and 500 GHz

Challenges in Measuring Firearm Prevalence: A Test of Cook\u27s Index Across The Rural–Urban Continuum

Cook\u27s Index is the most commonly used proxy for firearm prevalence. This research uses New York\u27s Pistol Permits to measure legitimate firearm prevalence and compare it to Cook\u27s Index. In this study, Cook\u27s Index predicted impossible values for several counties that together contained a clear majority of New York State citizens. Cook\u27s Index was also shown to be unreliable across types of counties. Rural and Urban counties had significantly different ratios of Cook\u27s Index to Pistol Permits in New York. The models show a general finding that the relationship between Cook\u27s Index and legitimate firearm ownership varies depending on the Rural-Urban Continuum. A more precise and non-linear model is needed to estimate the prevalence of firearms. Finally, the way in which Rural and Urban culture affect the use of firearms needs further research

Assessing personality in San Joaquin kit fox in situ: efficacy of field-based experimental methods and implications for conservation management

Utilisation of animal personality has potential benefit for conservation management. Due to logistics of robust behavioural evaluation in situ, the majority of studies on wild animals involve taking animals into captivity for testing, potentially compromising results. Three in situ tests for evaluation of boldness in San Joaquin kit fox (Vulpes macrotis mutica) were developed (ENOT: extended novel object test; RNOT: rapid novel object test; TH: trap/handling test). Each test successfully identified variation in boldness within its target age class(es). The TH test was suitable for use across all age classes. Tests were assessed for in situ suitability and for quantity/quality of data yielded. ENOT was rated as requiring high levels of time, cost and labour with greater likelihood of failure. However, it was rated highly for data quantity/quality. The TH test was rated as requiring little time, labour and cost, but yielding lower quality data. RNOT was rated in the middle. Each test had merit and could be adapted to suit project or species constraints. We recommend field-based evaluation of personality, reducing removal of animals from the wild and facilitating routine incorporation of personality assessment into conservation projects

Two-junction tuning circuits for submillimeter SIS mixers

The capacitance of superconducting tunnel junctions can seriously degrade the performance of quasiparticle (SIS) mixers operating in the submillimeter band, so it is essential to provide a circuit for tuning out this capacitance at the operating frequency. In this article, we present two new tuning circuits for SIS mixers which use a pair of SIS junctions connected by an inductance. Compared to previously proposed tuning circuits, ours have a broader bandwidth, are easier to scale to higher frequencies, and may be easier to fabricate. We have constructed quasi-optical mixers which employ these tuning circuits, using Nb/Al-Oxide/Nb SIS junctions defined by optical lithography. The performance of these devices is excellent, giving receiver noise temperatures of 113 K (DSB) at 490 GHz and 230 K DSB at 612 GHz. In addition to demonstrating the effectiveness of our tuning circuit, these results show that quasi-optical mixers can be competitive with or superior to waveguide mixers at submillimeter wavelengths. The mixers continue to perform well at frequencies up to 672 GHz, which is about 95% of the Nb gap frequency

Fault tolerant graphs, perfect hash functions and disjoint paths

Given a graph G on n nodes the authors say that a graph T on n + k nodes is a k-fault tolerant version of G, if one can embed G in any n node induced subgraph of T. Thus T can sustain k faults and still emulate G without any performance degradation. They show that for a wide range of values of n, k and d, for any graph on n nodes with maximum degree d there is a k-fault tolerant graph with maximum degree O(kd). They provide lower bounds as well: there are graphs G with maximum degree d such that any k-fault tolerant version of them has maximum degree at least Ω(d√k

Five Lenses on Team Tutor Challenges: A Multidisciplinary Approach

This chapter describes five disciplinary domains of research or lenses that contribute to the design of a team tutor. We focus on four significant challenges in developing Intelligent Team Tutoring Systems (ITTSs), and explore how the five lenses can offer guidance for these challenges. The four challenges arise in the design of team member interactions, performance metrics and skill development, feedback, and tutor authoring. The five lenses or research domains that we apply to these four challenges are Tutor Engineering, Learning Sciences, Science of Teams, Data Analyst, and Human–Computer Interaction. This matrix of applications from each perspective offers a framework to guide designers in creating ITTSs