Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults.

A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development

The American Invasion of Europe: The Long Term Rise in Overseas Travel, 1820-2000

Tourism today is an activity of substantial economic importance worldwide, and has been for some time. Tourism is also of substantial economic importance in the United States, sufficient to warrant the Bureau of Economic Analysis's establishing special accounts on travel and tourism. In this paper we investigate the long term rise in overseas travel by Americans. Over the course of the nineteenth and twentieth centuries the number of Americans going abroad rose from less than 2,000 travelers to over 26 million. The industry went from one confined to the elite of American society to what some have described as mass tourism. We document this rise by compiling a long term series on overseas travel, and describe the changes in the composition of the travelers, their destinations, and their mode of travel. We use an Error Correction Model to explain how the increase came about.

Simple Penning Ion Source for Laboratory Research and Development Applications

A simple Penning ion generator (PIG) that can be easily fabricated with simple machining skills and standard laboratory accessories is described. The PIG source uses an iron cathode body, samarium cobalt permanent magnet, stainless steel anode, and iron cathode faceplate to generate a plasma discharge that yields a continuous 1 mA beam of positively charged hydrogen ions at 1 mTorr of pressure. This operating condition requires 5.4 kV and 32.4 W of power. Operation with helium is similar to hydrogen. The ion source is being designed and investigated for use in a sealed-tube neutron generator; however, this ion source is thoroughly described so that it can be easily implemented by other researchers for other laboratory research and development applications

Macroeconomic Modeling of Tax Policy: A Comparison of Current Methodologies

The macroeconomic effects of tax reform are a subject of significant discussion and controversy. In 2015, the House of Representatives adopted a new “dynamic scoring” rule requiring a point estimate within the budget window of the deficit effect due to the macroeconomic response to certain proposed tax legislation. The revenue estimates provided by the staff of the Joint Committee on Taxation (JCT) for major tax bills often play a critical role in Congressional deliberations and public discussion of those bills. The JCT has long had macroeconomic analytic capability, and in recent years, responding to Congress’ interest in macrodynamic estimates for purposes of scoring legislation, outside think tank groups — notably the Tax Policy Center and the Tax Foundation — have also developed macrodynamic estimation models. The May 2017 National Tax Association (NTA) Spring Symposium brought together the JCT with the Tax Foundation and the Tax Policy Center for a panel discussion regarding their respective macrodynamic estimating approaches. This paper reports on that discussion. Below each organization provides a general description of their macrodynamic modeling methodology and answers five questions posed by the convening authors

Portable X-Ray Fluorescence Spectroscopy for Rapid and Cost-Effective Determination of Elemental Composition of Ground Forage

The recent development of portable X-ray fluorescence spectrometers (PXRF) has created new avenues for rapid plant elemental concentration determination at reduced cost while avoiding hazardous chemicals. A few studies have indicated the potential use of PXRF for homogenous plant tissue analysis. However, there is a lack of information for analysis of heterogeneous plant samples like livestock forage, which consists of a mixture of several species and plant parts, each varying in elemental concentration. Our objective was to evaluate PXRF for forage analysis, specifically the effect of forage particle size and scan time on important elements including P, K, Ca, and Fe determination. Hay samples (n = 42) were oven dried (60◦C for 3 days) and ground into three particle sizes (≤0.5 mm, 0.25–0.5 mm and 1–2 mm). Prepared samples were scanned by PXRF using a vacuum (\u3c10 torr) without a filter. Samples were placed in cups over thin prolene X-ray film and scanned for 180 s. A subset (n = 29) were also scanned for 60 and 120 s. PXRF counts for P, K, Ca, and Fe were compared with laboratory Inductively Coupled Plasma Optical Emission Spectroscopy (ICP) determinations, using regression models. Results indicated that these elements could potentially be determined with PXRF (r 2 ≥ 0.70) in heterogeneous forage samples. Relationship strength increased with decreasing particle size, however, the relationship was still strong (r 2 ≥ 0.57) at the largest particle size. Scanning time did not affect the relationship with ICP concentration for any of the particle sizes evaluated. This work demonstrated that with the right sample preparation PXRF can obtain results comparable to acid digestion and ICP regardless of sample composition, and suggests the potential for in situ determination

Northwest Africa 5298: A Basaltic Shergottite

NWA 5298 is a single 445 g meteorite found near Bir Gandouz, Morocco in March 2008 [1]. This rock has a brown exterior weathered surface instead of a fusion crust and the interior is composed of green mineral grains with interstitial dark patches containing small vesicles and shock melts [1]. This meteorite is classified as a basaltic shergottite [2]. A petrologic study of this Martian meteorite is being carried out with electron microprobe analysis and soon trace element analyses by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Oxygen fugacity is calculated from Fe-Ti oxides pairs in the sample. The data from this study constrains the petrogenesis of basaltic shergottites

Reverse total shoulder arthroplasty with proximal bone loss: a biomechanical comparison of partially vs. fully cemented humeral stems

BackgroundThe appropriate amount of cementation at the time of reverse total shoulder arthroplasty with significant proximal bone loss or resection is unknown. Extensive cementation of a humeral prosthesis makes eventual revision arthroplasty more challenging, increasing the risk of periprosthetic fracture. We analyzed the degree of subsidence and torque tolerance of humeral components undergoing standard cementation technique vs. our reduced polymethyl methacrylate (PMMA) protocol. Reduced cementation may provide sufficient biomechanical stability to resist physiologically relevant loads, while still permitting a clinically attainable torque for debonding the prosthesis.MethodsA total of 12 cadaveric humeri (6 matched pairs) underwent resection of 5 cm of bone distal to the greater tuberosity. Each pair of humeri underwent standard humeral arthroplasty preparation followed by either cementation using a 1.5-cm PMMA sphere at a location 3 cm inferior to the porous coating or standard full stem cementation. A 6-degree-of-freedom robot was used to perform all testing. Each humeral sample underwent 200 cycles of abduction, adduction, and forward elevation while being subjected to a physiologic compression force. Next, the samples were fixed in place and subjected to an increasing torque until implant-cement separation or failure occurred. Paired t tests were used to compare mean implant subsidence vs. a predetermined 5-mm threshold, as well as removal torque in matched samples.ResultsFully and partially cemented implants subsided 0.49 mm (95% CI 0.23-0.76 mm) and 1.85 mm (95% CI 0.41-3.29 mm), respectively, which were significantly less than the predetermined 5-mm threshold (P < .001 and P < .01, respectively). Removal torque between fully cemented stems was 45.22 Nm (95% CI 21.86-68.57 Nm), vs. 9.26 Nm (95% CI 2.59-15.93 Nm) for partially cemented samples (P = .021). Every fully cemented humerus fractured during implant removal vs. only 1 in the reduced-cementation group. The mean donor age in our study was 76 years (range, 65-80 years). Only 1 matched pair of humeri belonged to a female donor with comorbid osteoporosis. The fractured humerus in the partially cemented group belonged to that donor.ConclusionPartially and fully cemented humeral prostheses had subsidence that was significantly less than 5 mm. Partially cemented stems required less removal torque for debonding of the component from the cement mantle. In all cases, removal of fully cemented stems resulted in humeral fracture. Reduced cementation of humeral prostheses may provide both sufficient biomechanical stability and ease of future component removal

Identification of a Core Amino Acid Motif within the α Subunit of GABAARs that Promotes Inhibitory Synaptogenesis and Resilience to Seizures

The fidelity of inhibitory neurotransmission is dependent on the accumulation of γ-aminobutyric acid type A receptors (GABAARs) at the appropriate synaptic sites. Synaptic GABAARs are constructed from α(1-3), β(1-3), and γ2 subunits, and neurons can target these subtypes to specific synapses. Here, we identify a 15-amino acid inhibitory synapse targeting motif (ISTM) within the α2 subunit that promotes the association between GABAARs and the inhibitory scaffold proteins collybistin and gephyrin. Using mice in which the ISTM has been introduced into the α1 subunit (Gabra1-2 mice), we show that the ISTM is critical for axo-axonic synapse formation, the efficacy of GABAergic neurotransmission, and seizure sensitivity. The Gabra1-2 mutation rescues seizure-induced lethality in Gabra2-1 mice, which lack axo-axonic synapses due to the deletion of the ISTM from the α2 subunit. Taken together, our data demonstrate that the ISTM plays a critical role in promoting inhibitory synapse formation, both in the axonic and somatodendritic compartments