Summary Background Although the germicidal properties of ultraviolet (UV) light have long been known, it is only comparatively recently that the antimicrobial properties of visible violet–blue 405 nm ...light have been discovered and used for environmental disinfection and infection control applications. Aim To review the antimicrobial properties of 405 nm light and to describe its application as an environmental decontamination technology with particular reference to disinfection of the hospital environment. Methods Extensive literature searches for relevant scientific papers and reports. Findings A large body of scientific evidence is now available that provides underpinning knowledge of the 405 nm light-induced photodynamic inactivation process involved in the destruction of a wide range of prokaryotic and eukaryotic microbial species, including resistant forms such as bacterial and fungal spores. For practical application, a high-intensity narrow-spectrum light environmental disinfection system (HINS-light EDS) has been developed and tested in hospital isolation rooms. The trial results have demonstrated that this 405 nm light system can provide continuous disinfection of air and exposed surfaces in occupied areas of the hospital, thereby substantially enhancing standard cleaning and infection control procedures. Conclusion Violet–blue light, particularly 405 nm light, has significant antimicrobial properties against a wide range of bacterial and fungal pathogens and, although germicidal efficacy is lower than UV light, this limitation is offset by its facility for safe, continuous use in occupied environments. Promising results on disinfection efficacy have been obtained in hospital trials but the full impact of this technology on reduction of healthcare-associated infection has yet to be determined.
Inactivation of
Escherichia coli is examined using ultra-violet (UV) radiation from a pulsed xenon flashlamp. The light from the discharge has a broadband emission spectrum extending from the UV to ...the infrared region with a rich UV content. The flashlamp provides high-energy UV output using a small number of short-duration pulses (30
μs). The flashlamp is used with a monochromator to investigate the wavelength sensitivity of
E. coli to inactivation by the pulsed UV light. Using 8
nm wide pulses of UV radiation, the most efficient inactivation is found to occur at around 270
nm and no inactivation is observed above 300
nm. A pyroelectric detector allows the energy dose to be determined at each wavelength, and a peak value for
E. coli population reduction of 0.43 log per mJ/cm
2 is measured at 270
nm. The results are compared with the published data available for continuous UV light sources.
Here, absolute cross sections for the addition of s- and d-wave neutrons to 14C and 14N have been determined simultaneously via the (d,p) reaction at 10 MeV/u. The difference between the neutron and ...proton separation energies, ΔS, is around -20 MeV for the 14C+n system and +8 MeV for 14N+n. The population of the 1s1/2 and 0d5/2 orbitals for both systems is reduced by a factor of approximately 0.5 compared with the independent single-particle model, or about 0.6 when compared with the shell model. This finding strongly contrasts with results deduced from intermediate-energy knockout reactions between similar nuclei on targets of 9Be and 12C. The simultaneous technique used removes many systematic uncertainties.
We report an organophotocatalytic, N–CH3-selective oxidation of trialkylamines in continuous flow. Based on the 9,10-dicyanoanthracene (DCA) core, a new catalyst (DCAS) was designed with solubilizing ...groups for flow processing. This allowed O2 to be harnessed as a sustainable oxidant for late-stage photocatalytic N–CH3 oxidations of complex natural products and active pharmaceutical ingredients bearing functional groups not tolerated by previous methods. The organophotocatalytic gas–liquid flow process affords cleaner reactions than in batch mode, in short residence times of 13.5 min and productivities of up to 0.65 g per day. Spectroscopic and computational mechanistic studies showed that catalyst derivatization not only enhanced solubility of the new catalyst compared to poorly-soluble DCA, but profoundly diverted the photocatalytic mechanism from singlet electron transfer (SET) reductive quenching with amines toward energy transfer (EnT) with O2.
The nuclei below lead but with more than 126 neutrons are crucial to an understanding of the astrophysical r process in producing nuclei heavier than A∼190. Despite their importance, the structure ...and properties of these nuclei remain experimentally untested as they are difficult to produce in nuclear reactions with stable beams. In a first exploration of the shell structure of this region, neutron excitations in ^{207}Hg have been probed using the neutron-adding (d,p) reaction in inverse kinematics. The radioactive beam of ^{206}Hg was delivered to the new ISOLDE Solenoidal Spectrometer at an energy above the Coulomb barrier. The spectroscopy of ^{207}Hg marks a first step in improving our understanding of the relevant structural properties of nuclei involved in a key part of the path of the r process.
This study assessed the effects of high-intensity violet light on selected yeast and mould fungi. Cell suspensions of Saccharomyces cerevisiae, Candida albicans, and dormant and germinating spores ...(conidia) of the mould Aspergillus niger were exposed to high-intensity narrow band violet light with peak output at 405 nm generated from a light-emitting diode (LED) array. All three fungal species were inactivated by the 405-nm light without a requirement for addition of exogenous photosensitiser chemicals. Of the fungal species tested, S. cerevisiae was most sensitive and dormant conidia of A. niger were most resistant to 405-nm light exposure. Five-log10 colony forming units per millilitre (CFU ml−1) reductions of the tested species required exposure doses of 288 J cm−2 for S. cerevisiae, 576 J cm−2 for C. albicans, and a much higher value of 2.3 kJ cm−2 for dormant conidia of A. niger. During germination, A. niger conidia became more sensitive to 405-nm light exposure and sensitivity increased as germination progressed over an 8 h test period. Light exposure under aerobic and anaerobic conditions, together with results obtained using ascorbic acid as a scavenger of reactive oxygen species, revealed that 405-nm light inactivation in fungi involved an oxygen-dependent mechanism, as previously described in bacteria. The inactivation results achieved with yeast cells and fungal spores together with operational advantages associated with the use of a visible (nonultraviolet (UV)) light source highlight the potential of 405-nm light for fungal decontamination applications.
•Violet light shown to inactivate yeasts and dormant and germinating fungal spores.•A. niger dormant spores were most resistant to 405 nm violet light exposure.•A. niger conidia become more sensitive to 405 nm light as germination progresses.•Exposure tests demonstrated 405-nm light inactivation of fungi is oxygen-dependent.
Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear. tBID, the caspase-activated form of a ..."BH3-domain-only" BCL-2 family member, triggers the homooligomerization of "multidomain" conserved proapoptotic family members BAK or BAX, resulting in the release of cytochrome c from mitochondria. We find that cells lacking both Bax and Bak, but not cells lacking only one of these components, are completely resistant to tBID-induced cytochrome c release and apoptosis. Moreover, doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin. Thus, activation of a "multidomain" proapoptotic member, BAX or BAK, appears to be an essential gateway to mitochondrial dysfunction required for cell death in response to diverse stimuli.
The incidence of Barrett's esophagus (BE)-associated esophageal adenocarcinoma (EAC) is increasing. Next-generation sequencing (NGS) provides an unprecedented opportunity to uncover genomic ...alterations during BE pathogenesis and progression to EAC, but treatment-naive surgical specimens are scarce. The objective of this study was to establish the feasibility of using widely available endoscopic mucosal biopsies for successful NGS, using samples obtained from a BE 'progressor'. Paired-end whole-genome NGS was performed on the Illumina platform using libraries generated from mucosal biopsies of normal squamous epithelium (NSE), BE and EAC obtained from a patient who progressed to adenocarcinoma during endoscopic surveillance. Selective validation studies, including Sanger sequencing, immunohistochemistry and functional assays, were performed to confirm the NGS findings. NGS identified somatic nonsense mutations of AT-rich interactive domain 1A (SWI like) (ARID1A) and PPIE and an additional 37 missense mutations in BE and/or EAC, which were confirmed by Sanger sequencing. ARID1A mutations were detected in 15% (3/20) high-grade dysplasia (HGD)/EAC patients. Immunohistochemistry performed on an independent archival cohort demonstrated ARID1A protein loss in 0% (0/76), 4.9% (2/40), 14.3% (4/28), 16.0% (8/50) and 12.2% (12/98) of NSE, BE, low-grade dysplasia, HGD and EAC tissues, respectively, and was inversely associated with nuclear p53 accumulation (P=0.028). Enhanced cell growth, proliferation and invasion were observed on ARID1A knockdown in EAC cells. In addition, genes downstream of ARID1A that potentially contribute to the ARID1A knockdown phenotype were identified. Our studies establish the feasibility of using mucosal biopsies for NGS, which should enable the comparative analysis of larger 'progressor' versus 'non-progressor' cohorts. Further, we identify ARID1A as a novel tumor-suppressor gene in BE pathogenesis, reiterating the importance of aberrant chromatin in the metaplasia-dysplasia sequence.
Persistent pathogens have evolved to avoid elimination by the mammalian immune system including mechanisms to evade complement. Infections with African trypanosomes can persist for years and cause ...human and animal disease throughout sub-Saharan Africa. It is not known how trypanosomes limit the action of the alternative complement pathway. Here we identify an African trypanosome receptor for mammalian factor H, a negative regulator of the alternative pathway. Structural studies show how the receptor binds ligand, leaving inhibitory domains of factor H free to inactivate complement C3b deposited on the trypanosome surface. Receptor expression is highest in developmental stages transmitted to the tsetse fly vector and those exposed to blood meals in the tsetse gut. Receptor gene deletion reduced tsetse infection, identifying this receptor as a virulence factor for transmission. This demonstrates how a pathogen evolved a molecular mechanism to increase transmission to an insect vector by exploitation of a mammalian complement regulator.