Facilitation of a rapid response by self-amplifying mRNA vaccines

Recent advancements have demonstrated that vaccines based on self-amplifying mRNA have the potential to combine the positive attributes of other types of vaccines without their limitations. The synthetic production methods for their manufacture, combined with the modern tools of bioinformatics and synthetic biology, enable these vaccines to be produced rapidly from an electronic gene sequence. Hence, this approach could permit the concept of vaccines on demand as a rapid response to a real threat rather than the deployment of strategic stockpiles based on epidemiological predictions for possible threats. Although the mRNA vaccine field is in its infancy, the prospects are promising and proof of principle has been established in a variety of preclinical animal models

Alternative Energy Choices, Conservation, and Management: A Primer for Advanced Manufacturing Managers

Manufacturing managers need to understand the interrelated links between advanced manufacturing technology, primary and alternative energy choices, energy output values and costs, and energy conservation over the life of a project. Through an overview of these topics and the manager’s energy conservation processing optimization model developed in this paper, manufacturing managers, engineering technologists, and academics gain greater insight to the impacts of energy technologies upon manufacturing activities

The Malcolm Baldrige Award: What Technology Managers Can Learn From Health Care Winners

The Malcolm Baldrige Award is the highest presidential award for quality in the United States. Since 2002 there have been 28 winners of the award: eight from the health care field and four from the manufacturing category. This study identifies significant characteristics of health care award winners that can translate into exceptional quality and revenue performance for technology managers in manufacturing

Evolving Trends: An Environmental Scan on Design For Manufacturing Techniques

Abstract Design for Manufacturing (DFM) is a proactive design methodology used by many designers and engineers to reduce and control manufacturing costs. Through the review of several periodicals, magazines, journals, textbooks, television newscasts, radio announcements, manager interviews conducted by the author (Manager A, B, & C), and websites, a trend may be established on "Design for Manufacturing" and manufacturing in general. Coded manager and company names were used for confidentiality reasons. The environmental scan presented highlights DFM and other manufacturing issues from 2002 through 2007. This study establishes a baseline for engineering technology scholars assessing DFM techniques in the next five or ten years. Literature Review El Wakil (1998) defines "Design for Manufacturing" as a relatively simple process involving design personnel initially considering the methods of manufacture during the design phase of a new product. In fact, design is considered one part of a three-part pyramid, with materials and manufacturing as the other two parts. Within this pyramid, a manufacturing system is brought into existence; a system constructed to deliver well-conceived ideas (inputs) into wellconstructed products (outputs). The key to DFM is the intermingling of design and manufacturing technologies and capabilities in order to produce a product at the lowest possible cost with the highest possible quality as is accepted by the end-user; a.k.a. "The Customer." To further emphasize the role of the design engineer in facilitating DFM, the following paragraph from "The design engineer must, of course, know that certain manufacturing processes and operations exist that can manufacture the desired product. However, merely knowing that feasible processes exist is not sufficient. The designer must also know their limitations, relative costs, and process capabilities (accuracy, tolerance requirements, etc.) in order to design for manufacture. If maximum economy is to be achieved, th

Structural characteristics correlate with immune responses induced by HIV envelope glycoprotein vaccines

AbstractHIV envelope glycoprotein (Env) is the target for inducing neutralizing antibodies. Env is present on the virus surface as a trimer, and, upon binding to CD4, a cascade of events leads to structural rearrangement exposing the co-receptor binding site and entry into the CD4+ host target cells. We have designed monomeric and trimeric Env constructs with and without deletion of the variable loop 2 (ΔV2) from SF162, a subtype B primary isolate, and performed biophysical, biochemical and immunological studies to establish a potential structure–functional relationship. We expressed these Envs in CHO cells, purified the proteins to homogeneity and performed biophysical studies to define the binding properties to CD4, structural characteristics and exposure of epitopes recognized by b12 and CD4i mAb (17B) on both full-length and mutant HIV Env proteins. Parameters evaluated include oligomerization state, number and affinity of CD4 binding sites, enthalpy and entropy of the Env–CD4 interaction and affinity for b12 and 17b mAbs. We observed one CD4 binding site per monomer and three active CD4 binding sites per trimer. A 40-fold difference in affinity of the gp120 monomer vs. the o-gp140 trimer towards CD4 was observed (Kd = 58 nM and 1.5 nM, respectively), whereas only a 2-fold difference was observed for the V2 deleted Envs (Kd of gp120ΔV2 = 19 nM, Kd of o-gp140DV2 = 9.3 nM). Monomers had 3-fold higher affinity to the mAb 17b and at least 3-fold weaker affinity to b12 compared to trimers, with gp120DV2 having the weakest affinity for b12 (Kd = 446 nM). Affinity of CD4 binding correlated with proportion of the antibodies induced against the conformational epitopes by the corresponding Envs, and changes in mAb binding correlated with the induction of antibodies directed against linear epitopes. Furthermore, biophysical analysis reveals that the V2 deletion has broad structural implications in the monomer not shared by the trimer, and these changes are reflected in the quality of the immune responses induced in rabbits. These data suggest that biophysical characteristics of HIV Env, such as affinity for CD4, and exposure of important neutralizing epitopes, such as those recognized by b12 mAb, may be important predictors of its in vivo efficacy and may serve as important surrogate markers for screening Env structures as potential vaccine candidates

PTF10iya: A short-lived, luminous flare from the nuclear region of a star-forming galaxy

We present the discovery and characterisation of PTF10iya, a short-lived (dt ~ 10 d, with an optical decay rate of ~ 0.3 mag per d), luminous (M_g ~ -21 mag) transient source found by the Palomar Transient Factory. The ultraviolet/optical spectral energy distribution is reasonably well fit by a blackbody with T ~ 1-2 x 10^4 K and peak bolometric luminosity L_BB ~ 1-5 x 10^44 erg per s (depending on the details of the extinction correction). A comparable amount of energy is radiated in the X-ray band that appears to result from a distinct physical process. The location of PTF10iya is consistent with the nucleus of a star-forming galaxy (z = 0.22405 +/- 0.00006) to within 350 mas (99.7 per cent confidence radius), or a projected distance of less than 1.2 kpc. At first glance, these properties appear reminiscent of the characteristic "big blue bump" seen in the near-ultraviolet spectra of many active galactic nuclei (AGNs). However, emission-line diagnostics of the host galaxy, along with a historical light curve extending back to 2007, show no evidence for AGN-like activity. We therefore consider whether the tidal disruption of a star by an otherwise quiescent supermassive black hole may account for our observations. Though with limited temporal information, PTF10iya appears broadly consistent with the predictions for the early "super-Eddington" phase of a solar-type star disrupted by a ~ 10^7 M_sun black hole. Regardless of the precise physical origin of the accreting material, the large luminosity and short duration suggest that otherwise quiescent galaxies can transition extremely rapidly to radiate near the Eddington limit; many such outbursts may have been missed by previous surveys lacking sufficient cadence.Comment: 18 pages, 8 figures; revised following referee's comment

Lower extremity compartment syndrome in the acute care surgery paradigm: safety lessons learned

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens