The glucocorticoid PYED-1 disrupts mature biofilms of Candida spp. and inhibits hyphal development in Candida albicans

Invasive Candida infections have become a global public health problem due to the increase of Candida species resistant against antifungal therapeutics. The glucocorticoid PYED-1 (pregnadiene-11-hydroxy-16α,17α-epoxy-3,20-dione-1) has antimicrobial activity against various bacterial taxa. Consequently, it might be considered for the treatment of Candida infections. The antifungal activity of PYED-1 was evaluated against several fungal strains that were representative of the five species that causes the majority of Candida infections—namely, Candida albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis and Candida krusei. PYED-1 exhibited a weak antifungal activity and a fungistatic effect on all five Candida species. On the other hand, PYED-1 exhibited a good antibiofilm activity, and was able to eradicate the preformed biofilms of all Candida species analyzed. Moreover, PYED-1 inhibited germ tube and hyphae formation of C. albicans and reduced adhesion of C. albicans to abiotic surfaces by up to 30%

N-nonyloxypentyl-l-deoxynojirimycin inhibits growth, biofilm formation and virulence factors expression of Staphylococcus aureus

Staphylococcus aureus is one of the major causes of hospital-and community-associated bacterial infections throughout the world, which are difficult to treat due to the rising number of drug-resistant strains. New molecules displaying potent activity against this bacterium are urgently needed. In this study, d-and l-deoxynojirimycin (DNJ) and a small library of their N-alkyl derivatives were screened against S. aureus ATCC 29213, with the aim to identify novel candidates with inhibitory potential. Among them, N-nonyloxypentyl-l-DNJ (l-NPDNJ) proved to be the most active compound against S. aureus ATCC 29213 and its clinical isolates, with the minimum inhibitory concentration (MIC) value of 128 µg/mL. l-NPDNJ also displayed an additive effect with gentamicin and oxacillin against the gentamicin-and methicillin-resistant S. aureus isolate 00717. Sub-MIC values of l-NPDNJ affected S. aureus biofilm development in a dose-dependent manner, inducing a strong reduction in biofilm biomass. Moreover, real-time reverse transcriptase PCR analysis revealed that l-NPDNJ effectively inhibited at sub-MIC values the transcription of the spa, hla, hlb and sea virulence genes, as well as the agrA and saeR response regulator genes

Histochemical analysis of glycoconjugates in the domestic cat testis

The localization and characterization of oligosaccharide sequences in the cat testis was investigated using 12 lectins in combination with the ßelimination reaction, N-Glycosidase F and sialidase digestion. Leydig cells expressed O-linked glycans with terminal aGalNAc (HPA reactivity) and N-glycans with terminal/internal aMan (Con A affinity). The basement membrane showed terminal Neu5Aca2,6Gal/GalNAc, Galß1,3GalNAc, a/ßGalNAc, and GlcNAc (SNA, PNA, HPA, SBA, GSA II reactivity) in O-linked oligosaccharides, terminal Galß1,4GlcNAc (RCA120 staining) and aMan in N-linked oligosaccharides; in addition, terminal Neu5Aca2,3Galß1,4GlcNac, Forssman pentasaccharide, aGal, aL-Fuc and internal GlcNAc (MAL II, DBA, GSA I-B4, UEA I, KOH-sialidase-WGA affinity) formed both O- and N-linked oligosaccharides. The Sertoli cells cytoplasm contained terminal Neu5Ac- Galß1,4GlcNAc, Neu5Ac-ßGalNAc as well as internal GlcNAc in O-linked glycans, aMan in N-linked glycoproteins and terminal Neu5Aca2,6Gal/ GalNAc in both O- and N-linked oligosaccharides. Spermatogonia exhibited cytoplasmic N-linked glycoproteins with aMan residues. The spermatocytes cytoplasm expressed terminal Neu5Aca2,3Galß1,4 GlcNAc and Galß1,3GalNAc in O-linked oligosaccharides, terminal Galß1,4GlcNAc and a/ßGalNAc in N-linked glycoconjugates. The Golgi region showed terminal Neu5aca2,3Galß1,4GlcNac, Galß1,4GlcNAc, Forssman pentasaccharide, and aGalNAc in O-linked oligosaccharides, aMan and terminal ßGal in N-linked oligosaccharides. The acrosomes of Golgi-phase spermatids expressed terminal Galß1,3GalNAc, Galß1,4GlcNAc, Forssmann pentasaccharide, a/ßGalNAc, aGal and internal GlcNAc in O-linked oligosaccharides, terminal a/ßGalNAc, aGal and terminal/internal aMan in N-linked glycoproteins. The acrosomes of cap-phase spermatids lacked internal Forssman pentasaccharide and aGal, while having increased a/ßGalNAc. The acrosomes of elongated spermatids did not show terminal Galß1,3GalNAc, displayed terminal Galß1,4GlcNAc and a/ßGalNAc in N-glycans and Neu5Ac-Galß1,3GalNAc in O-linked oligosaccharides

Robust Model Predictive Control of An Input Delayed Functional Electrical Stimulation

Functional electrical stimulation (FES) is an external application of low-level currents to elicit muscle contractions that can potentially restore limb function in persons with spinal cord injury. However, FES often leads to the rapid onset of muscle fatigue, which limits performance of FES-based devices due to reduction in force generation capability. Fatigue is caused by unnatural muscle recruitment and synchronous and repetitive recruitment of muscle fibers. In this situation, overstimulation of the muscle fibers further aggravates the muscle fatigue. Therefore, a motivation exists to use optimal controls that minimize muscle stimulation while providing a desired performance. Model predictive controller (MPC) is one such optimal control method. However, the traditional MPC is dependent on exact model knowledge of the musculoskeletal dynamics and cannot handle modeling uncertainties. Motivated to address modeling uncertainties, robust MPC approach is used to control FES. Moreover, two new robust MPC techniques are studied to address electromechanical delay (EMD) during FES, which often causes performance issues and stability problems. This thesis compares two types of robust MPCs: a Lyapunov-based MPC and a tube- based MPC for controlling knee extension elicited through FES. Lyapunov-based MPC incorporated a contractive constraint that bounds the Lyapunov function of the MPC with a Lyapunov function that was used to derive an EMD compensation control law. The Lyapunov-based MPC was simulated to validate its performance. In the tube-based MPC, the EMD compensation controller was chosen to be the tube that eliminated output of the nominal MPC and the output of the real system. Regulation experiments were performed for the tube-based MPC on a leg extension machine and the controller showed robust performance despite modeling uncertainties

Imaging the warped dusty disk wind environment of SU Aurigae with MIRC-X

SU Aurigae is a widely studied T Tauri star and here we present original state-of-the-art interferometric observations with better uv and baseline coverage than previous studies. We aim to investigate the characteristics of the circumstellar material around SU Aur, constrain the disk geometry, composition and inner dust rim structure. The MIRC-X instrument at CHARA is a 6 telescope optical beam combiner offering baselines up to 331 m. We undertook image reconstruction for model-independent analysis, and fitted geometric models such as Gaussian and ring distributions. Additionally, the fitting of radiative transfer models constrains the physical parameters of the disk. Image reconstruction reveals a highly inclined disk with a slight asymmetry consistent with inclination effects obscuring the inner disk rim through absorption of incident star light on the near-side and thermal re-emission/scattering of the far-side. Geometric models find that the underlying brightness distribution is best modelled as a Gaussian with a FWHM of $1.53\pm0.01 \mathrm{mas}$ at an inclination of $56.9\pm0.4^\circ$ and minor axis position angle of $55.9\pm0.5^\circ$. Radiative transfer modelling shows a flared disk with an inner radius at 0.16 au which implies a grain size of $0.14 \mathrm{\mu m}$ assuming astronomical silicates and a scale height of 9.0 au at 100 au. In agreement with literature, only the dusty disk wind successfully accounts for the NIR excess by introducing dust above the mid-plane. Our results confirm and provide better constraints than previous inner disk studies of SU Aurigae. We confirm the presence of a dusty disk wind in the cicumstellar environment, the strength of which is enhanced by a late infall event which also causes very strong misalignments between the inner and outer disks.Comment: arXiv admin note: substantial text overlap with arXiv:2111.06205, arXiv:1905.1190

Characterising the orbit and circumstellar environment of the high-mass binary MWC 166 A

Context: Stellar evolution models are highly dependent on accurate mass estimates, especially for high-mass stars in the early stages of evolution. The most direct method for obtaining model-independent masses is derivation from the orbit of close binaries. Aims: To derive the first astrometric+RV orbit solution for the single-lined spectroscopic binary MWC 166 A, based on CHARA and VLTI near-infrared interferometry over multiple epochs and ~100 archival radial velocity measurements, and to derive fundamental stellar parameters from this orbit. We also sought to model circumstellar activity in the system from K-band spectral lines. Methods: We geometrically modelled the dust continuum to derive astrometry at 13 epochs and constrain individual stellar parameters. We used the continuum models as a base to examine differential phases, visibilities and closure phases over the Br-$\gamma$ and He-I emission lines. Results: Our orbit solution suggests a period of $367.7\pm0.1$ d, twice as long as found with previous RV orbit fits, subsequently constraining the component masses to $M_1=12.2\pm2.2 M_\odot$ and $M_2=4.9\pm0.5 M_\odot$. The line-emitting gas was found to be localised around the primary and is spatially resolved on scales of ~11 stellar radii, with the spatial displacement between the line wings consistent with a rotating disc. Conclusions: The large radius and stable orientation of the line emission are inconsistent with magnetospheric or boundary-layer accretion, but indicate an ionised inner gas disk around MWC 166 Aa. We observe line variability that could be explained either with generic line variability in a Herbig star disc or V/R variations in a decretion disc. We also constrained the age of the system to ~$(7\pm2)\times10^5$ yr, consistent with the system being comprised of a main-sequence primary and a secondary still contracting towards the main sequence.Comment: 24 pages, 19 figures, 7 tables, 1 appendix. Accepted in A&

Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: propensity-score matching analysis and TIL evaluation

Background The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted. Methods Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/- Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias. Results In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade >= 3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05). Conclusions We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/- Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure

Working With the Tangible: Radiation, A Twenty-First Century Interpretation

The intangible means of expression was a topic of investigation across various disciplines when Michael Chekhov was developing his pedagogic practice. In the world of science, Harold Saxton Burr and Albert Szent-Gyorgi, were examining the body as a conductor of energy. Their research was relevant to Chekhov's approach regarding how the actor communicates with internal and external stimulus. This article begins with an analysis of Chekhov's theories on Radiation, it moves on to offer insights into science and energy work with reference to cell Biologist James Oschman and his concept of ‘the living matrix’ and Mae Wan Ho's critique of quantum cohesion. Examples of praxis demonstrate that contemporary science and body work can provide a greater understanding of how Radiation and the organisation of energy can enhance performance

La Rete sismica Mobile in telemetria satellitare (Re.Mo.Tel.)

Oggi la nuova Rete Sismica Mobile in telemetria satellitare” (Re.Mo.Tel.) è composta da nove stazioni la cui trasmissione, tramite ponte UHF (Ultra High Frequency), è equamente ripartita verso tre centri di acquisizione intermedi, detti “sottonodi”). Tali sottonodi, a loro volta tramite connessione Wi-Fi, ridirezionano il flusso dati verso un “centro stella” (detto “nodo”) dal quale, con il sistema di trasmissione satellitare Libra VSAT Nanometrics, i dati sono inviati al centro acquisizione dati della Sala Sorveglianza Sismica della sede INGV di Roma e ridondati al centro “disaster recovery” approntato presso l’Osservatorio di Grottaminarda (Sede Irpinia in provincia di Avellino). La struttura della Re.Mo.Tel. è stata ideata ed ingegnerizzata in modo da ridurre al minimo i tempi d’installazione. Il sistema è stato infatti realizzato interamente “plug and play” e di conseguenza nessuna attività di configurazione è richiesta all’operatore all’atto dell’istallazione. La Re.Mo.Tel. si basa su di un articolato sistema di trasmissione (UHF, Wi-Fi e satellitare), mediante l’impiego di diversi apparati