Alien Registration- Brewer, Philip B. (Allagash, Aroostook County)

https://digitalmaine.com/alien_docs/32803/thumbnail.jp

A technique for chronic repuncture micropuncture of dog kidney

The precision of kidney micropuncture for exploring changes in glomerular and tubular function was strikingly enhanced by the introduction of the repuncture and re-collection technique [1], thus permitting the use of each tubule as its own control. This procedure has allowed detection of changes in function that were not appreciated previously. However, the technical design of re-collection micropuncture is such that it is mainly applicable to the study of rapid and usually massive changes in homeostasis; exploration of the renal response to chronic, more physiologic maneuvers has been limited to clearance and non-repuncture micropuncture studies.This paper describes a technique for chronic repuncture micropuncture that allows repeat proximal tubule sampling in dogs at an interval of up to 14 days

High-Affinity Small Molecule Inhibitors of T Cell Costimulation: Compounds for Immunotherapy

SummaryCostimulatory molecules are important regulators of T cell activation and thus favored targets for therapeutic manipulation of immune responses. One of the key costimulatory receptors is CD80, which binds the T cell ligands, CD28, and CTLA-4. We describe a set of small compounds that bind with high specificity and low nanomolar affinity to CD80. The compounds have relatively slow off-rates and block both CD28 and CTLA-4 binding, implying that they occlude the shared ligand binding site. The compounds inhibit proinflammatory cytokine release in T cell assays with submicromolar potency, and as such, they represent promising leads for the development of novel therapeutics for immune-mediated inflammatory disease. Our results also suggest that other predominantly β proteins, such as those that dominate the cell surface, may also be accessible as potentially therapeutic targets

Implementing Electronic Tablet-Based Education of Acute Care Patients

Poor education-related discharge preparedness for patients with heart failure is believed to be a major cause of avoidable rehospitalizations. Technology-based applications offer innovative educational approaches that may improve educational readiness for patients in both inpatient and outpatient settings; however, a number of challenges exist when implementing electronic devices in the clinical setting. Implementation challenges include processes for "on-boarding" staff, mediating risks of cross-contamination with patients' device use, and selling the value to staff and health system leaders to secure the investment in software, hardware, and system support infrastructure. Strategies to address these challenges are poorly described in the literature. The purpose of this article is to present a staff development program designed to overcome challenges in implementing an electronic, tablet-based education program for patients with heart failure

Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor

The blood-brain barrier (BBB) is a critical structure that serves as the gatekeeper between the central nervous system and the rest of the body. It is the responsibility of the BBB to facilitate the entry of required nutrients into the brain and to exclude potentially harmful compounds; however, this complex structure has remained difficult to model faithfully in vitro. Accurate in vitro models are necessary for understanding how the BBB forms and functions, as well as for evaluating drug and toxin penetration across the barrier. Many previous models have failed to support all the cell types involved in the BBB formation and/or lacked the flow-created shear forces needed for mature tight junction formation. To address these issues and to help establish a more faithful in vitro model of the BBB, we have designed and fabricated a microfluidic device that is comprised of both a vascular chamber and a brain chamber separated by a porous membrane. This design allows for cell-to-cell communication between endothelial cells, astrocytes, and pericytes and independent perfusion of both compartments separated by the membrane. This NeuroVascular Unit (NVU) represents approximately one-millionth of the human brain, and hence, has sufficient cell mass to support a breadth of analytical measurements. The NVU has been validated with both fluorescein isothiocyanate (FITC)-dextran diffusion and transendothelial electrical resistance. The NVU has enabled in vitro modeling of the BBB using all human cell types and sampling effluent from both sides of the barrier

LATERAL BRANCHING OXIDOREDUCTASE acts in the final stages of strigolactone biosynthesis inArabidopsis

Strigolactones are a group of plant compounds of diverse but related chemical structures. They have similar bioactivity across a broad range of plant species, act to optimize plant growth and development, and promote soil microbe interactions. Carlactone, a common precursor to strigolactones, is produced by conserved enzymes found in a number of diverse species. Versions of the MORE AXILLARY GROWTH1 (MAX1) cytochrome P450 from rice and Arabidopsis thaliana make specific subsets of strigolactones from carlactone. However, the diversity of natural strigolactones suggests that additional enzymes are involved and remain to be discovered. Here, we use an innovative method that has revealed a missing enzyme involved in strigolactone metabolism. By using a transcriptomics approach involving a range of treatments that modify strigolactone biosynthesis gene expression coupled with reverse genetics, we identified LATERAL BRANCHING OXIDOREDUCTASE (LBO), a gene encoding an oxidoreductase-like enzyme of the 2-oxoglutarate and Fe(II)-dependent dioxygenase superfamily. Arabidopsis lbo mutants exhibited increased shoot branching, but the lbo mutation did not enhance the max mutant phenotype. Grafting indicated that LBO is required for a graft-transmissible signal that, in turn, requires a product of MAX1. Mutant lbo backgrounds showed reduced responses to carlactone, the substrate of MAX1, and methyl carlactonoate (MeCLA), a product downstream of MAX1. Furthermore, lbo mutants contained increased amounts of these compounds, and the LBO protein specifically converts MeCLA to an unidentified strigolactone-like compound. Thus, LBO function may be important in the later steps of strigolactone biosynthesis to inhibit shoot branching in Arabidopsis and other seed plants

Different paths to the modern state in Europe: the interaction between domestic political economy and interstate competition

Theoretical work on state formation and capacity has focused mostly on early modern Europe and on the experience of western European states during this period. While a number of European states monopolized domestic tax collection and achieved gains in state capacity during the early modern era, for others revenues stagnated or even declined, and these variations motivated alternative hypotheses for determinants of fiscal and state capacity. In this study we test the basic hypotheses in the existing literature making use of the large date set we have compiled for all of the leading states across the continent. We find strong empirical support for two prevailing threads in the literature, arguing respectively that interstate wars and changes in economic structure towards an urbanized economy had positive fiscal impact. Regarding the main point of contention in the theoretical literature, whether it was representative or authoritarian political regimes that facilitated the gains in fiscal capacity, we do not find conclusive evidence that one performed better than the other. Instead, the empirical evidence we have gathered lends supports to the hypothesis that when under pressure of war, the fiscal performance of representative regimes was better in the more urbanized-commercial economies and the fiscal performance of authoritarian regimes was better in rural-agrarian economie

Minimum requirements for publishing hydrogen, carbon, nitrogen, oxygen and sulfur stable-isotope delta results (IUPAC Technical Report)

Stable hydrogen, carbon, nitrogen, oxygen and sulfur (HCNOS) isotope compositions expressed as isotope-delta values are typically reported relative to international standards such as Vienna Standard Mean Ocean Water (VSMOW), Vienna Peedee belemnite (VPDB) or Vienna Cañon Diablo Troilite (VCDT). These international standards are chosen by convention and the calibration methods used to realise them in practice undergo occasional changes. To ensure longevity and reusability of published data, a comprehensive description of (1) analytical procedure, (2) traceability, (3) data processing, and (4) uncertainty evaluation is required. Following earlier International Union of Pure and Applied Chemistry documents on terminology and notations, this paper proposes minimum requirements for publishing HCNOS stable-isotope delta results. Each of the requirements are presented with illustrative example

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN