Characterization of VRC01, a potent and broadly neutralizing anti-HIV mAb, produced in transiently and stably transformed tobacco

The proposed clinical trial in Africa of VRC01, a potent broadly neutralizing antibody (bNAb) capable of neutralizing 91% of known HIV-1 isolates, raises concerns about testing a treatment which will be too expensive to be accessible by the most important target population, the poor in under-developed regions such as sub-Saharan Africa. Here, we report the expression of VRC01 in plants as an economic alternative to conventional mammalian-cell-based production platforms. The heavy and light chain genes of VRC01 were cloned onto a single vector, pTRAk.2, which was transformed into Nicotiana benthamiana or Nicotiana tabacum using transient and stable expression production systems respectively. VRC01 has been successfully expressed transiently in plants with expression level of approximately 80 mg antibody/kg; stable transgenic lines expressing up to 100 mg antibody/kg were also obtained. Plant-produced VRC01 from both systems showed a largely homogeneous N-glycosylation profile with a single dominant glycoform. The binding kinetics to gp120 IIIB (approximately 1 nM), neutralization of HIV-1 BaL or a panel of 10 VRC01-sensitive HIV-1 Env pseudoviruses of VRC01 produced in transient and stable plants were also consistent with VRC01 from HEK cells

What is the clinical relevance of different lung compartments?

The lung consists of at least seven compartments with relevance to immune reactions. Compartment 1 - the bronchoalveolar lavage (BAL), which represents the cells of the bronchoalveolar space: From a diagnostic point of view the bronchoalveolar space is the most important because it is easily accessible in laboratory animals, as well as in patients, using BAL. Although this technique has been used for several decades it is still unclear to what extent the BAL represents changes in other lung compartments. Compartment 2 - bronchus-associated lymphoid tissue (BALT): In the healthy, BALT can be found only in childhood. The role of BALT in the development of the mucosal immunity of the pulmonary surfaces has not yet been resolved. However, it might be an important tool for inhalative vaccination strategies. Compartment 3 - conducting airway mucosa: A third compartment is the bronchial epithelium and the submucosa, which both contain a distinct pool of leukocytes (e.g. intraepithelial lymphocytes, IEL). This again is also accessible via bronchoscopy. Compartment 4 - draining lymph nodes/Compartment 5 - lung parenchyma: Transbronchial biopsies are more difficult to perform but provide access to two additional compartments - lymph nodes with the draining lymphatics and lung parenchyma, which roughly means "interstitial" lung tissue. Compartment 6 - the intravascular leukocyte pool: The intravascular compartment lies between the systemic circulation and inflamed lung compartments. Compartment 7 - periarterial space: Finally, there is a unique, lung-specific space around the pulmonary arteries which contains blood and lymph capillaries. There are indications that this "periarterial space" may be involved in the pulmonary host defense

Carbon radio recombination lines from gigahertz to megahertz frequencies towards Orion A

Context. The combined use of carbon radio recombination lines (CRRLs) and the 158 $\mu$m-[CII] line is a powerful tool for the study of the energetics and physical conditions (e.g., temperature and density) of photodissociation regions (PDRs). However, there are few observational studies that exploit this synergy. Aims. Here we explore the relation between CRRLs and the 158 $\mu$m-[CII] line in light of new observations and models. Methods. We present new and existing observations of CRRLs in the frequency range 0.15--230 GHz with ALMA, VLA, the GBT, Effelsberg 100m, and LOFAR towards Orion~A (M42). We complement these observations with SOFIA observations of the 158 $\mu$m-[CII] line. We studied two PDRs: the foreground atomic gas, known as the Veil, and the dense PDR between the HII region and the background molecular cloud. Results. In the Veil we are able to determine the gas temperature and electron density, which we use to measure the ionization parameter and the photoelectric heating efficiency. In the dense PDR, we are able to identify a layered PDR structure at the surface of the molecular cloud to the south of the Trapezium cluster. There we find that the radio lines trace the colder portion of the ionized carbon layer, the C$^{+}$/C/CO interface. By modeling the emission of the $158$~$\mu$m-[CII] line and CRRLs as arising from a PDR we derive a thermal pressure $>5\times10^{7}$ K cm$^{-3}$ and a radiation field $G_{0}\approx10^{5}$ close to the Trapezium. Conclusions. This work provides additional observational support for the use of CRRLs and the 158 $\mu$m-[CII] line as complementary tools to study dense and diffuse PDRs, and highlights the usefulness of CRRLs as probes of the C$^{+}$/C/CO interface.Comment: 18 pages, 16 figures, accepted for publication in A&

Remarks on transverse RMS emittance

This report presents some considerations on the radial rms emittance of linear accelerator beams. In case of acceleration, a constant normalized rms emittance results if each beam particle is described by the same linear differential equation. The second part shows how the rms emittance varies if the beam particles have a distribution in betatron frequency of approximately the nominal value

Recruitment and baseline characteristics of the Community of Voices choir study to promote the health and well-being of diverse older adults.

Objective:To describe the recruitment and baseline results of the Community of Voices study that aims to examine the effect of a community choir intervention on the health and well-being of older adults from diverse racial/ethnic and socioeconomic backgrounds. Method:Using community-based participatory research methods, we recruited adults age 60 and over from 12 Administration on Aging-supported senior centers in San Francisco into a 2-arm cluster-randomized controlled trial of the community choir intervention. Multiple outreach methods were used. We tracked outreach, screening, and recruitment metrics and collected demographics and baseline outcomes via community-based, interviewer-administered surveys and performance measures of cognition, physical function, and psychosocial variables. Results:The study contacted 819 individuals, screened 636, and enrolled 390 diverse older adults over a 42-month, phased recruitment period. The mean age was 71.2 (SD = 7.3), and the majority were women. Two-thirds of the sample are non-white, and 20% of participants reported having financial hardship. Discussion:Outreach and recruitment methods used in the Community of Voices trial facilitated enrollment of a large proportion of minority and lower-SES older adults in the final sample. Similar recruitment approaches could serve as a model for recruiting diverse racial/ethnic and socioeconomic older adults into research

Attosecond counter-rotating-wave effect in xenon driven by strong fields

We investigate the subfemtosecond dynamics of a highly excited xenon atom coherently driven by a strong control field at which the Rabi frequency of the system is comparable to the frequency of a driving laser. The widely used rotating-wave approximation breaks down at such fields, resulting in features such as the counter-rotating-wave (CRW) effect. We present a time-resolved observation of the CRW effect in the highly excited 4d-1np xenon using attosecond transient absorption spectroscopy. Time-dependent many-body theory confirms the observation and explains the various features of the absorption spectrum seen in experiment. ?2017 American Physical Society.111Ysciescopu