Association of hydrophobically-modified poly(ethylene glycol) with fusogenic liposomes

AbstractWe present results on using cooperative interactions to shield liposomes by incorporating multiple hydrophobic anchoring sites on polyethylene glycol (PEG) polymers. The hydrophobically-modified PEGs (HMPEGs) are comb-graft polymers with strictly alternating monodisperse PEG blocks (Mw=6, 12, or 35 kDa) bonded to C18 stearylamide hydrophobes. Cooperativity is varied by changing the degree of oligomerization at a constant ratio of PEG to stearylamide. Fusogenic liposomes prepared from N-C12-DOPE:DOPC 7:3 (mol:mol) were equilibrated with HMPEGs. Affinity for polymer association to liposomes increases with the degree of oligomerization; equilibrium constants (given as surface coverage per equilibrium concentration of free polymer) for 6 kDa PEG increased from 6.1±0.8 (mg/m2)/(mg/ml) for 2.5 loops to 78.1±12.2 (mg/m2)/(mg/ml) for 13 loops. In contrast, the equilibrium constant for distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG5k) was 0.4±0.1 (mg/m2)/(mg/ml).The multi-loop HMPEGs demonstrate higher levels of protection from complement binding than DSPE-PEG5k. Greater protection does not correlate with binding strength alone. The best shielding was by HMPEG6k-DP3 (with three 6 kDa PEG loops), suggesting that PEG chains with adequate surface mobility provide optimal protection from complement opsonization. Complement binding at 30 min and 12 h demonstrates that protection by multi-looped PEGs is constant whereas DSPE-PEG5k initially protects but presumably partitions off of the surface at longer times

Relation of neurohumoral activation to clinical variables and degree of ventricular dysfunction: A report from the registry of studies of left ventricular dysfunction

Objectives. This study examined the relation between neurohumoral activation and severity of left ventricular dysfunction and congestive heart failure in a broad group of patients with depressed left ventricular function who were not recruited on the basis of eligibility for a therapeutic trial. Background. Previous studies have established the presence of neurohumoral activation in patients with severe congestive heart failure. It is not known whether the activation of these neurohumoral mechanisms is related to an impairment in left ventricular function

β-Herpesviruses in Febrile Children with Cancer

These viruses should be included in the differential diagnosis of febrile disease

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

Ungrading : why rating students undermines learning (and what to do instead)

Comprend un index"The moment is right for critical reflection on what has been assumed to be a core part of schooling. In Ungrading, fifteen educators write about their diverse experiences going gradeless. Some contributors are new to the practice and some have been engaging in it for decades. Some are in humanities and social sciences, some in STEM fields. Some are in higher education, but some are the K-12 pioneers who led the way. Based on rigorous and replicated research, this is the first book to show why and how faculty who wish to focus on learning, rather than sorting or judging, might proceed. It includes honest reflection on what makes ungrading challenging, and testimonials about what makes it transformative. CONTRIBUTORS: Aaron Blackwelder Susan D. Blum Arthur Chiaravalli Gary Chu Cathy N. Davidson Laura Gibbs Christina Katopodis Joy Kirr Alfie Kohn Christopher Riesbeck Starr Sackstein Marcus Schultz-Bergin Clarissa Sorensen-Unruh Jesse Stommel John Warner"--(ProQuest

Comparative Evaluation of Three Commercial Systems for Nucleic Acid Extraction from Urine Specimens

A nucleic acid extraction system that can handle small numbers of specimens with a short test turnaround time and short hands-on time is desirable for emergent testing. We performed a comparative validation on three systems: the MagNA Pure compact system (Compact), the NucliSens miniMAG extraction instrument (miniMAG), and the BioRobot EZ1 system (EZ1). A total of 75 urine specimens submitted for polyomavirus BK virus detection were used. The human β-actin gene was detected on 75 (100%), 75 (100%), and 72 (96%) nucleic acid extracts prepared by the miniMAG, EZ1, and Compact, respectively. The miniMAG produced the highest quantity of nucleic acids and the best precision among the three systems. The agreement rate was 100% for BKV detection on nucleic acid extracts prepared by the three extraction systems. When a full panel of specimens was run, the hands-on time and test turnaround time were 105.7 and 121.1 min for miniMAG, 6.1 and 22.6 min for EZ1, and 7.4 and 33.7 min for Compact, respectively. The EZ1 and Compact systems processed automatic nucleic acid extraction properly, providing a good solution to the need for sporadic but emergent specimen detection. The miniMAG yielded the highest quantity of nucleic acids, suggesting that this system would be the best for specimens containing a low number of microorganisms of interest