Antibody-based therapies for emerging infectious diseases.

In the 19th century, it was discovered that immune sera were useful in treating infectious diseases. Serum therapy was largely abandoned in the 1940s because of the toxicity associated with the administration of heterologous sera and the introduction of effective antimicrobial chemotherapy. Recent advances in the technology of monoclonal antibody production provide the means to generate human antibody reagents and reintroduce antibody therapies, while avoiding the toxicities associated with serum therapy. Because of the versatility of antibodies, antibody-based therapies could, in theory, be developed against any existing pathogen. The advantages of antibody-based therapies include versatility, low toxicity, pathogen specificity, enhancement of immune function, and favorable pharmacokinetics; the disadvantages include high cost, limited usefulness against mixed infections, and the need for early and precise microbiologic diagnosis. The potential of antibodies as antiinfective agents has not been fully tapped. Antibody-based therapies constitute a potentially useful option against newly emergent pathogens

Design and Experimental Validation of a Software-Defined Radio Access Network Testbed with Slicing Support

Network slicing is a fundamental feature of 5G systems to partition a single network into a number of segregated logical networks, each optimized for a particular type of service, or dedicated to a particular customer or application. The realization of network slicing is particularly challenging in the Radio Access Network (RAN) part, where multiple slices can be multiplexed over the same radio channel and Radio Resource Management (RRM) functions shall be used to split the cell radio resources and achieve the expected behaviour per slice. In this context, this paper describes the key design and implementation aspects of a Software-Defined RAN (SD-RAN) experimental testbed with slicing support. The testbed has been designed consistently with the slicing capabilities and related management framework established by 3GPP in Release 15. The testbed is used to demonstrate the provisioning of RAN slices (e.g. preparation, commissioning and activation phases) and the operation of the implemented RRM functionality for slice-aware admission control and scheduling

Mucosal Vaccines, Sterilizing Immunity, and the Future of SARS-CoV-2 Virulence

Sterilizing immunity after vaccination is desirable to prevent the spread of infection from vaccinees, which can be especially dangerous in hospital settings while managing frail patients. Sterilizing immunity requires neutralizing antibodies at the site of infection, which for respiratory viruses such as SARS-CoV-2 implies the occurrence of neutralizing IgA in mucosal secretions. Systemic vaccination by intramuscular delivery induces no or low-titer neutralizing IgA against vaccine antigens. Mucosal priming or boosting, is needed to provide sterilizing immunity. On the other side of the coin, sterilizing immunity, by zeroing interhuman transmission, could confine SARS-CoV-2 in animal reservoirs, preventing spontaneous attenuation of virulence in humans as presumably happened with the endemic coronaviruses. We review here the pros and cons of each vaccination strategy, the current mucosal SARS-CoV-2 vaccines under development, and their implications for public health

Dual cobalt – copper light-driven catalytic reduction of aldehydes and aromatic ketones in aqueous media

We present an efficient, general, fast, and robust light-driven methodology based on earth-abundant elements to reduce aryl ketones, and both aryl and aliphatic aldehydes (up to 1400 TON). The catalytic system consists of a robust and well-defined aminopyridyl cobalt complex active for photocatalytic water reduction and the [Cu(bathocuproine)(Xantphos)](PF6) photoredox catalyst. The dual cobalt–copper system uses visible light as the driving-force and H2O and an electron donor (Et3N or iPr2EtN) as the hydride source. The catalytic system operates in aqueous mixtures (80–60% water) with high selectivity towards the reduction of organic substrates (>2000) vs. water reduction, and tolerates O2. High selectivity towards the hydrogenation of aryl ketones is observed in the presence of terminal olefins, aliphatic ketones, and alkynes. Remarkably, the catalytic system also shows unique selectivity for the reduction of acetophenone in the presence of aliphatic aldehydes. The catalytic system provides a simple and convenient method to obtain α,β-deuterated alcohols. Both the observed reactivity and the DFT modelling support a common cobalt hydride intermediate. The DFT modelled energy profile for the [Co–H] nucleophilic attack to acetophenone and water rationalises the competence of [CoII–H] to reduce acetophenone in the presence of water. Mechanistic studies suggest alternative mechanisms depending on the redox potential of the substrate. These results show the potential of the water reduction catalyst [Co(OTf)(Py2Tstacn)](OTf) (1), (Py2Tstacn = 1,4-di(picolyl)-7-(p-toluenesulfonyl)-1,4,7-triazacyclononane, OTf = trifluoromethanesulfonate anion) to develop light-driven selective organic transformations and fine solar chemicals

A stitch in time saves nine: closing the hole after removal of the aortic root cannula

<p>Abstract</p> <p>Background</p> <p>On completion of the surgical procedure the hole in the ascending aorta has to be closed after withdrawal of the aortic root cannula. The aorta is usually pinched by a double transversal stitch or it is crumpled by a purse string suture. Nevertheless, hemostasis is difficult to obtain because closure is done under recovered pressure. Additional stitches buttressed with teflon-felt pledgets are often required. Unfortunately, sensitivity to bacterial implantation and the proximity to the sternotomy line could make the foreign material of the pledgets responsible for chronic infections and fistulas.</p> <p>Methods</p> <p>Two simple square stitches orthogonal to each other could be a very useful suture combining simplicity with effectiveness. To do this, two 4-0 polypropylene half-threads are put obliquely through the full thickness of the aortic wall, to and fro with inverse obliquities. Each of them draws a cross inside the aortic wall and two sides of a square outside. As a result a little square is drawn by the threads around the hole.</p> <p>Results</p> <p>For years we have never needed to reinforce the closure by supplemental stitches with hundreds of patients.</p> <p>Conclusion</p> <p>This type of closure has some advantages. In contrast to common stitches the aortic wall is not bent, crumpled or deformed, bites pass all aortic layers and the crossing of the threads covers the hole from inside rather than outside. Moreover, each thread can be tied with half of the tension required by other sutures because the two stitches act together but in the opposite direction. Finally, the technique is speedy and it requires only two half-threads. Most importantly, there is no need for teflon-felt pledgets. As a result, we have no longer seen any type of chronic infection or fistula.</p

Experimental modulation of capsule size in Cryptococcus neoformans

Experimental modulation of capsule size is an important technique for the study of the virulence of the encapsulated pathogen Cryptococcus neoformans. In this paper, we summarize the techniques available for experimental modulation of capsule size in this yeast and describe improved methods to induce capsule size changes. The response of the yeast to the various stimuli is highly dependent on the cryptococcal strain. A high CO(2) atmosphere and a low iron concentration have been used classically to increase capsule size. Unfortunately, these stimuli are not reliable for inducing capsular enlargement in all strains. Recently we have identified new and simpler conditions for inducing capsule enlargement that consistently elicited this effect. Specifically, we noted that mammalian serum or diluted Sabouraud broth in MOPS buffer pH 7.3 efficiently induced capsule growth. Media that slowed the growth rate of the yeast correlated with an increase in capsule size. Finally, we summarize the most commonly used media that induce capsule growth in C. neoformans

Redaction of sensitive data in the publication of dual use research of concern

Editorial. The publication of scientific information that derives from dual use research of concern (DURC) poses major problems for journals because it brings into conflict the benefits of free access to data and the need to prevent misuse of that information by others. Recently, a group of authors and a major scientific journal addressed the issue of publishing information on a newly discovered, highly lethal toxin that can be delivered to large populations and for which there are no available countermeasures. The journal addressed this conflict by permitting the redaction of information that is normally considered essential for publication. This action establishes a precedent for redaction of sensitive data that also provides an example of responsible scientific publishing. However, this precedent leaves many questions unanswered and suggests a need for a discussion by all stakeholders of scientific information so as to derive normative standards for the publication of DURC

The Nuclearization of Biology Is a Threat to Health and Security

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78142/1/bsp.2009.0047.pd

Biodefense Research: A Win-Win Challenge

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63273/1/bsp.2008.1114.pd