All-dielectric toroidal metasurfaces for angular-dependent resonant polarization beam splitting

An all-dielectric metasurface exhibiting a strong toroidal resonance is theoretically designed and experimentally demonstrated as an angular-dependent resonant polarization beam-splitter in the microwave K-band. The metasurface is fabricated by embedding a square periodic array of high-permittivity ceramic cuboid resonators in a 3D-printed substrate of polylactic acid. It is demonstrated that by properly selecting the resonator geometry and by tuning the angle of incidence through mechanical rotation, the metasurface can switch between a polarization beam splitting and bandpass or bandstop operation. Such performance is achieved by exploiting the highly asymmetric Fano spectral profile of the toroidal resonance and the very low (high) dispersion of the associated p-(s-) polarized mode resulting from the resonant toroidal dipole mode's field profile, as evidenced by both full-wave and band structure simulations. Theoretically infinite extinction ratios are achievable for polarization beam splitting operation with very low insertion losses and adjustable bandwidth. The experimental demonstration of such a compact, all-dielectric metasurface expands the research portfolio of resonant metasurfaces toward not only the investigation of the intriguing physics of toroidal modes but also to the engineering of functional millimeter-wave components for polarization control, for instance, in the context of 5G wireless communication networks.This research was co-financed by the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH CREATE INNOVATE (Project code: No. T1EDK-02784) and by the Comunidad de Madrid and FEDER Program (S2018/NMT-4326), the Ministerio de Economía y Competitividad of Spain (TEC2016-77242-C3-1-R and TEC2016-76021-C2-2-R), and the FEDER/Ministerio de Ciencia, Innovación y Universidades and Agencia Estatal de Investigación (RTC2017-6321-1, PID2019-107270RB-C21 and PID2019-109072RB-C31)

Structural studies of T4S systems by electron microscopy

Abstract: Type IV secretion (T4S) systems are large dynamic nanomachines that transport DNA and/or proteins through the membranes of bacteria. Analysis of T4S system architecture is an extremely challenging task taking into account their multi protein organisation and lack of overall global symmetry. Nonetheless the last decade demonstrated an amazing progress achieved by X-ray crystallography and cryo-electron microscopy. In this review we present a structural analysis of this dynamic complex based on recent advances in biochemical, biophysical and structural studies

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

Development of a novel and automated fluorescent immunoassay for the analysis of beta-lactam antibiotics

An automated immunosensor for the rapid and sensitive analysis of penicillin type -lactam antibiotics has been developed and optimized. An immunogen was prepared by coupling the common structure of the penicillanic -lactam antibiotics, i.e., 6-aminopenicillanic acid to keyhole limpet hemocyanin. Polyclonal antibodies raised in rabbits after immunization with this conjugate have been applied for the development of a competitive fluoroimmunoassay (FIA), using a novel fluorescent penicillin {[2S,5R,6R]-3,3-dimethyl-7-oxo-6-[(pyren-1ylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxilic acid, PAAP} as the tracer and penicillin G as the reference antibiotic. Protein A/G covalently bound to an azlactone-activated polymeric support was used for the orientated capture of the antibody-antigen immunocomplexes. Upon desorption from the immunosupport, the emission signal generated by the PAAP-Ab complexes is related to the antibiotic concentration in the sample. The 50% binding inhibition concentration of penicillin G standard curves was at 30 ng mL-1 with a detection limit (10% binding inhibition) of 2.4 ng mL-1 and a dynamic range from 6.0 to 191 ng mL-1 (20-80% binding inhibition) penicillin G. The generic nature of the antiserum was shown by good relative cross-reactivities with penicillin type -lactam antibiotics such as amoxicillin (50%), ampicillin (47%), and penicillin V (145%) and a lower response to the isoxazolyl penicillins such as oxacillin, cloxacillin, and dicloxacillin. No cross-reactivity was obtained for cephalosporin type -lactam antibiotics (cephapirin), cloramphenicol, or fluoroquinolones (enrofloxacin and ciprofloxacin). The total analysis time was 23 min per determination, and the immunoreactor could be reused for more than 200 cycles without significant loss of activity. The immunosensor has been successfully applied to the direct analysis of penicillin G and amoxicillin in spiked influent and effluent sewage treatment plant water samples with excellent recoveries (mean values for penicillin G and amoxicillin, 99 and 105%, respectively). Results displayed by comparative analysis of the immunosensor with a chromatographic procedure for penicillins showed excellent agreement between both method

Molecular engineering of fluorescent penicillins for molecularly imprinted polymer assays

The interaction of seven novel fluorescent labeled beta-lactams with a library of six polymer materials molecularly imprinted (MI) with penicillin G (PenG) has been evaluated using both radioactive and fluorescence competitive assays. The highly fluorescent competitors (emission quantum yields of 0.4-0.95) have been molecularly engineered to contain pyrene or dansyl labels while keeping intact the 6-aminopenicillanic acid moiety for efficient recognition by the cross-linked polymers. Pyrenemethylacetamidopenicillanic acid (PAAP) is the tagged antibiotic that provides the highest selectivity when competing with PenG for the specific binding sites in a MI polymer prepared with methacrylic acid and trimethylolpropane trimethacrylate (10:15 molar ratio) in acetonitrile in the presence of PenG. Molecular modeling shows that recognition of the fluorescent analogues of PenG by the MI material is due to a combination of size and shape selectivity and demonstrates how critical the choice of label and tether chain is. PAAP has been applied to the development of a fluorescence competitive assay for PenG analysis with a dynamic range of 3-890 mu M in 99:1 acetonitrile-water solution. Competitive binding studies demonstrate various degrees of cross-reactivity for some antibiotics derived from 6-aminopenicillanic acid, particularly amoxicillin, ampicillin, and penicillin V (but not oxacillin, cloxacillin, dicloxacillin, or nafcillin). Other antibiotics, such as chloramphenicol, tetracycline, or cephapirin, do not compete with PAAP for binding to the imprinted polymer. The MI assay has successfully been tested for PenG analysis in a pharmaceutical formulation

Development of a novel and automated fluorescent immunoassay for the analysis of beta-lactam antibiotics

An automated immunosensor for the rapid and sensitive analysis of penicillin type -lactam antibiotics has been developed and optimized. An immunogen was prepared by coupling the common structure of the penicillanic -lactam antibiotics, i.e., 6-aminopenicillanic acid to keyhole limpet hemocyanin. Polyclonal antibodies raised in rabbits after immunization with this conjugate have been applied for the development of a competitive fluoroimmunoassay (FIA), using a novel fluorescent penicillin {[2S,5R,6R]-3,3-dimethyl-7-oxo-6-[(pyren-1ylacetyl)amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxilic acid, PAAP} as the tracer and penicillin G as the reference antibiotic. Protein A/G covalently bound to an azlactone-activated polymeric support was used for the orientated capture of the antibody-antigen immunocomplexes. Upon desorption from the immunosupport, the emission signal generated by the PAAP-Ab complexes is related to the antibiotic concentration in the sample. The 50% binding inhibition concentration of penicillin G standard curves was at 30 ng mL-1 with a detection limit (10% binding inhibition) of 2.4 ng mL-1 and a dynamic range from 6.0 to 191 ng mL-1 (20-80% binding inhibition) penicillin G. The generic nature of the antiserum was shown by good relative cross-reactivities with penicillin type -lactam antibiotics such as amoxicillin (50%), ampicillin (47%), and penicillin V (145%) and a lower response to the isoxazolyl penicillins such as oxacillin, cloxacillin, and dicloxacillin. No cross-reactivity was obtained for cephalosporin type -lactam antibiotics (cephapirin), cloramphenicol, or fluoroquinolones (enrofloxacin and ciprofloxacin). The total analysis time was 23 min per determination, and the immunoreactor could be reused for more than 200 cycles without significant loss of activity. The immunosensor has been successfully applied to the direct analysis of penicillin G and amoxicillin in spiked influent and effluent sewage treatment plant water samples with excellent recoveries (mean values for penicillin G and amoxicillin, 99 and 105%, respectively). Results displayed by comparative analysis of the immunosensor with a chromatographic procedure for penicillins showed excellent agreement between both method

InfoBiology by printed arrays of microorganism colonies for timed and on-demand release of messages

This paper presents a proof-of-principle method, called InfoBiology, to write and encode data using arrays of genetically engineered strains of Escherichia coli with fluorescent proteins (FPs) as phenotypic markers. In InfoBiology, we encode, send, and release information using living organisms as carriers of data. Genetically engineered systems offer exquisite control of both genotype and phenotype. Living systems also offer the possibility for timed release of information as phenotypic features can take hours or days to develop. We use growth media and chemically induced gene expression as cipher keys or “biociphers” to develop encoded messages. The messages, called Steganography by Printed Arrays of Microbes (SPAM), consist of a matrix of spots generated by seven strains of E. coli, with each strain expressing a different FP. The coding scheme for these arrays relies on strings of paired, septenary digits, where each pair represents an alphanumeric character. In addition, the photophysical properties of the FPs offer another method for ciphering messages. Unique combinations of excited and emitted wavelengths generate distinct fluorescent patterns from the Steganography by Printed Arrays of Microbes (SPAM). This paper shows a new form of steganography based on information from engineered living systems. The combination of bio- and “photociphers” along with controlled timed-release exemplify the capabilities of InfoBiology, which could enable biometrics, communication through compromised channels, easy-to-read barcoding of biological products, or provide a deterrent to counterfeiting

Adeno-associated virus liver transduction efficiency measured by in vivo [18F]FHBG positron emission tomography imaging in rodents and nonhuman primates

Recombinant adeno-associated virus 5 (rAAV5) represents a candidate vector with unique advantages for the treatment of hepatic disorders because of its narrow hepatic tropism. Noninvasive in vivo imaging of transgene expression provides an important tool with which to quantify the transduction efficiency, and duration and location, of transgene expression. In this study, we used positron emission tomography (PET) and positron emission tomography-computed tomography (PET-CT) imaging to monitor liver transduction efficacy in rodents and nonhuman primates that received rAAV5 vector encoding herpes simplex virus thymidine kinase (HSV-TK). HSV-TK expression in liver was also measured by immunohistochemistry. Notable differences in liver transduction efficiency were found, dependent on the animal species and sex. Male rodents were better transduced than females, as previously described. Moreover, male nonhuman primates also displayed increased hepatic expression of the rAAV5-delivered transgene, indicating that differences in rAAV-mediated liver transduction can be anticipated in humans. Our results demonstrate the high sensitivity and reproducibility of PET, using HSV-TK and [(18)F]FHBG, to detect gene expression after rAAV vector administration into living animals, confirming the utility of this technology in the quantification of transgene expression, even at low expression levels. However, we also describe how an immune response against HSV-TK hampered analysis of long-term expression in nonhuman primates