Nanoplastic Settling Potential in Saline Environments

Nanoplastics are produced industrially for uses such as cosmetics and also generated by erosion of consumer plastic products. Nanoplastic properties are largely unstudied; understanding how these particles act will allow us to evaluate their environmental impact, design methods of detection, and remediation. Microplastics bioaccumulate and absorb harmful chemicals. Smaller nano-sized plastics may have an even higher affinity for chemical adsorbtion due to high surface areas, making these tiny particles a contaminant of emerging concern.https://digitalcommons.mtech.edu/urp_aug_2017/1003/thumbnail.jp

Treatment of patients with chronic thrombo embolic pulmonary hypertension: focus on riociguat

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease of the pulmonary vascular bed that is characterized by elevations in the mean pulmonary artery pressure in the setting of perfusion defects on ventilation-perfusion scan, and subsequently confirmed by pulmonary angiography. CTEPH, or World Health Organization (WHO) group 4 pulmonary hypertension, is a result of unresolved thromboembolic obstruction in the pulmonary arteries. Pulmonary endarterectomy (PEA) is the treatment of choice for CTEPH as it is a potentially curative therapy. However, up to one-third of patients are not candidates for the surgery, either due to distal and inaccessible nature of the lesions or comorbid conditions. Due to remodeling that occurs in nonobstructed pulmonary vessels, a portion of patients who have undergone PEA have residual CTEPH after the procedure, attributable to high shear stress prior to PEA. This phenomenon has led to the understanding of a so-called two-compartment model of CTEPH, opening the door to pharmacologic treatment strategies. In 2013, riociguat, a soluble guanylate cyclase stimulator, was approved in the US and Europe for the treatment of inoperable or persistent/recurrent CTEPH. This article reviews the current management of CTEPH with a focus on riociguat

Designing and implementing auxiliary operational processes

Thesis (M.B.A.)--Massachusetts Institute of Technology, Sloan School of Management; and, (S.M.)--Massachusetts Institute of Technology, Engineering Systems Division; in conjunction with the Leaders for Manufacturing Program at MIT, 2008.Includes bibliographical references (p. 83-84).Amazon.com, one of the largest and most profitable online retailers, has been experiencing such dramatic growth rates that it must continually update and modify its fulfillment process in order to meet customer demand for its products. As the volume of customer orders increases, management at the different fulfillment centers must determine the optimal way to increase the throughput through their facility. Many times the answer lies in improving the primary process, but occasionally it makes better sense if an auxiliary process is built or expanded to meet the increased demand.This thesis analyzes the decision criteria necessary to determine when an auxiliary process should be designed in addition to an established primary process. The author's internship project will be presented as an example of how to implement such a secondary method. The six-month LFM project focused on increasing the Fernley, Nevada fulfillment center's capacity by making improvements to its manual sortation/packaging. This process, nicknamed BIGS, was originally built to offload large and troublesome orders from the primary, automated process path. The unique labor-intensive procedures used in this process held several advantages that justified its existence and the investments necessary to expand its capacityby Zachary R. Smith.S.M.M.B.A

Evolution of the complementary sex-determination gene of honey bees: Balancing selection and trans-species polymorphisms

The mechanism of sex determination varies substantively among evolutionary lineages. One important mode of genetic sex determination is haplodiploidy, which is used by ∼20% of all animal species, including >200,000 species of the entire insect order Hymenoptera. In the honey bee Apis mellifera, a hymenopteran model organism, females are heterozygous at the csd (complementary sex determination) locus, whereas males are hemizygous (from unfertilized eggs). Fertilized homozygotes develop into sterile males that are eaten before maturity. Because homozygotes have zero fitness and because common alleles are more likely than rare ones to form homozygotes, csd should be subject to strong overdominant selection and negative frequency-dependent selection. Under these selective forces, together known as balancing selection, csd is expected to exhibit a high degree of intraspecific polymorphism, with long-lived alleles that may be even older than the species. Here we sequence the csd genes as well as randomly selected neutral genomic regions from individuals of three closely related species, A. mellifera, Apis cerana, and Apis dorsata. The polymorphic level is approximately seven times higher in csd than in the neutral regions. Gene genealogies reveal trans-species polymorphisms at csd but not at any neutral regions. Consistent with the prediction of rare-allele advantage, nonsynonymous mutations are found to be positively selected in csd only in early stages after their appearances. Surprisingly, three different hypervariable repetitive regions in csd are present in the three species, suggesting variable mechanisms underlying allelic specificities. Our results provide a definitive demonstration of balancing selection acting at the honey bee csd gene, offer insights into the molecular determinants of csd allelic specificities, and help avoid homozygosity in bee breeding

438: SAFETY AND EFFICACY OF CEFEPIME INTRAVENOUS PUSH VERSUS PIGGYBACK IN GRAM-NEGATIVE BACTEREMIA

Introduction: Gram-negative infections including bacteremia are a major cause of inpatient mortality. Optimizing management is key to improving outcomes. Beta-lactams exhibit optimal antibacterial effects based on the time free concentrations exceed an organism’s minimum inhibitory concentration. Limited data exists assessing outcomes using beta-lactams as intravenous push (IVP) compared to intravenous piggyback (IVPB) in serious infections. This study’s purpose was to compare safety and efficacy of cefepime administered IVP versus IVPB in gram-negative bacteremia. Methods: This was an IRB-approved, retrospective cohort of patients hospitalized January 2014 to December 2021 and administered cefepime for \u3e48 hours for gram-negative bacteremia involving Pseudomonas aeruginosa or AmpC beta-lactamase producing bacteria. Two groups were included: one of patients who received cefepime IVPB and the second of patients who received cefepime IVP. The primary outcome was a desirability of outcome ranking (DOOR) on a five-point ordinal scale including clinical cure (no recurrent bacteremia of initial pathogen, antibiotic escalation, or 30-day in-hospital mortality) and neurologic adverse effects during cefepime treatment up to 30 days inpatient or at discharge. Secondary outcomes included antibiotic escalation, time to defervescence, vasopressor use, and in-hospital mortality. A sample of 127 patients per group provided 80% power. Data was analyzed using measures of central tendency and variability, chi-square, student’s T test, and Mann-Whitney U. Results: A total 254 patients were included with 127 per group. DOOR with clinical cure was similar between the IVPB and IVP groups (105 (82.7%) vs. 104 (81.9%); P=0.656). Escalation of therapy was the most common reason for clinical failure in both the IVPB and IVP groups (17 (13.4%) vs. 18 (14.2%); P=0.856). More patients in the IVP group required vasopressors (13 (10.2%) vs. 28 (22.0%); P=0.011). No difference was found in time to defervescence or in-hospital mortality. Conclusions: When compared to cefepime IVPB in gram-negative bacteremia, treatment with IVP showed no significant difference in instances of clinical cure or adverse effects. Further research in a more severely ill population is needed to evaluate safety and efficacy of cefepime IVPB versus IVP

Cutaneous Silent Period Characteristics are Dependent on the Organization of Upper Limb Muscles

abstractCutaneous silent periods (CSPs) are inhibitory spinal reflexes mediated by small diameter A-δ fibers, serving to protect the body from harmful stimuli (Leis et al., 1992; Kofler, 2003). Currently, CSPs are believed to only inhibit the extensor muscles of the upper limb halting motions such as reaching, while exciting flexor muscles to withdraw the limb. The present study sought to determine if CSPs could be evoked in both extensor and flexor muscles of the upper limb, thereby providing further insight into the organization of the spinal circuitry associated with this reflex. 22 subjects performed contractions with seven muscles from the hand, forearm, upper arm, and shoulder while muscle activity was recorded with electromyography. Subjects were electrically stimulated (10x perceptual threshold) with 20 individual pulses delivered to each digit II (radial nerve) and digit V (ulnar nerve) of the right hand during each contraction. Results demonstrated significant main effects (p<0.001) across muscles for the key dependent variables of the CSP: onsets (F[6,21] = 15.42, p <0.001), durations (F[6,21] = 65.39, p <0.001), and % of suppression (F[6,21] = 91, p <0.001), similarly for both nerves stimulated. Distal muscles presented with the earliest onset times, longest duration of inhibition, and largest amount of inhibition. Moving proximally, the onset times became later with duration and the amount of inhibition decreasing. Linear regressions showed that the distance of the muscle from the spinal cord (cm) was a significant predictor of the duration (digit II r2 = 0.43; digit V r2 = 0.46) and amount of inhibition (digit II r2 = 0.51; digit V r2 = 0.48). The results demonstrate the occurrence of CSPs throughout the upper limb, with the greatest inhibition of distal muscles, leading us to hypothesize that the corticospinal tract, specifically direct cortico-motorneuronal connections, are directly influenced by the inhibitory input

The E2 ubiquitin-conjugating enzymes UBE2D1 and UBE2D2 regulate VEGFR2 dynamics and endothelial function

Vascular endothelial growth factor receptor 2 (VEGFR2, encoded by KDR) regulates endothelial function and angiogenesis. VEGFR2 undergoes ubiquitination that programs this receptor for trafficking and proteolysis, but the ubiquitin-modifying enzymes involved are ill-defined. Herein, we used a reverse genetics screen for the human E2 family of ubiquitin-conjugating enzymes to identify gene products that regulate VEGFR2 ubiquitination and proteolysis. We found that depletion of either UBE2D1 or UBE2D2 in endothelial cells caused a rise in steady-state VEGFR2 levels. This rise in plasma membrane VEGFR2 levels impacted on VEGF-A-stimulated signalling, with increased activation of canonical MAPK, phospholipase Cγ1 and Akt pathways. Analysis of biosynthetic VEGFR2 is consistent with a role for UBE2D enzymes in influencing plasma membrane VEGFR2 levels. Cell-surface-specific biotinylation and recycling studies showed an increase in VEGFR2 recycling to the plasma membrane upon reduction in UBE2D levels. Depletion of either UBE2D1 or UBE2D2 stimulated endothelial tubulogenesis, which is consistent with increased VEGFR2 plasma membrane levels promoting the cellular response to exogenous VEGF-A. Our studies identify a key role for UBE2D1 and UBE2D2 in regulating VEGFR2 function in angiogenesis

E2 ubiquitin-conjugating enzymes, UBE2D1 and UBE2D2, regulate VEGFR2 dynamics and endothelial function

Vascular endothelial growth factor receptor 2 (VEGFR2) regulates endothelial function and angiogenesis. VEGFR2 undergoes ubiquitination which programs this receptor for trafficking and proteolysis but the ubiquitin-modifying enzymes involved are ill-defined. Herein, we used a reverse genetics screen of the human E2 family of ubiquitin-conjugating enzymes to identify gene products which regulate VEGFR2 ubiquitination and proteolysis. We find that depletion of either UBE2D1 or UBE2D2 in endothelial cells cause a rise in steady-state VEGFR2 levels. This rise in plasma membrane VEGFR2 levels impact on VEGF-A-stimulated signalling, with increased activation of canonical MAPK, phospholipase C1, and Akt pathways. Analysis of biosynthetic VEGFR2 is consistent with a role for UBE2D enzymes in influencing plasma membrane VEGFR2 levels. Cell surface biotinylation and recycling studies show an increase in VEGFR2 recycling to the plasma membrane upon reduction in UBE2D levels. Depletion of either UBE2D1 or UBE2D2 stimulates endothelial tubulogenesis which is consistent with increased VEGFR2 plasma membrane levels promoting the cellular response to exogenous VEGF-A. Our studies identify a key role for UBE2D1 and UBE2D2 in regulating VEGFR2 function in angiogenesis