Recent developments in filtration media and respirator technology in response to COVID-19.

Abstract: The COVID-19 pandemic triggered a surge in demand for N95 or equivalent respirators that the global supply chain was unable to satisfy. This shortage in critical equipment has inspired research that addresses the immediate problems and has accelerated the development of the next-generation filtration media and respirators. This article provides a brief review of the most recent work with regard to face respirators and filtration media. We discuss filtration efficiency of the widely utilized cloth masks. Next, the sterilization of and reuse of existing N95 respirators to extend the existing stockpile is discussed. To expand near-term supplies, optimization of current manufacturing methods, such as melt-blown processes and electrospinning, has been explored. Future manufacturing methods have been investigated to address long-term supply shortages. Novel materials with antiviral and sterilizable properties with the ability for multiple reuses have been developed and will contribute to the development of the next generation of longer lasting multi-use N95 respirators. Finally, additively manufactured respirators are reviewed, which enable a rapidly deployable source of reusable respirators that can use any filtration fabric.

Binder jet additive manufacturing method to fabricate near net shape crack-free highly dense Fe-6.5 wt.% Si soft magnets.

High silicon (Si) electrical steel has the potential for efficient use in applications such as electrical motors and generators with cost-effective in processing, but it is difficult to manufacture. Increasing the Si content beyond 3 wt.% improves magnetic and electrical properties, with 6.5 wt.% being achievable. The main goal of this research is to design, develop, and implement a scalable additive manufacturing process to fabricate Fe with 6.5 wt.% Si (Fe-6Si) steel with high magnetic permeability, high electrical resistivity, low coercivity, and low residual induction that other methods cannot achieve because of manufacturing limitations. Binder jet additive manufacturing was used to deposit near net shape components that were subsequently sintered via solid-state sintering to achieve near full densification. Here, it is shown that the use of solid-state sintering mitigates cracking since no rapid solidification occurs unlike fusion-based additive technologies. The Fe-6Si samples demonstrated an ultimate tensile strength of 434 MPa, electrical resistivity of 98 µΩ cm, and saturation magnetization of 1.83 T with low coercivity and high permeability. The results strongly supports to replace the only available 0.1 mm thick chemical vapor deposition (CVD) produced Si steel using the cost effective AM method with good mechanical and magnetic properties for motor applications.

Effects of the addition of boron nitride nanoplate on the fracture toughness, flexural strength, and Weibull Distribution of hydroxyapatite composites prepared by spark plasma sintering.

Hydroxyapatite (HA) has inherently low fracture toughness and low flexural strength, thus limiting it from wide scale application as an implant material in the biomedical field. To increase the fracture toughness and flexural strength, HA composites were fabricated by adding boron nitride nanoplatelets (BNNP) as reinforcement. Spark plasma sintering was utilized to achieve fine grain structure. The addition of BNNP facilitated grain size refinement. The BNNP reinforced HA composites exhibited increased fracture toughness (2.3 MPa m1/2) and flexural strength (79.79 MPa) of HA over previous published values (1.0 MPa m1/2). Despite that the Weibull Distribution indicated a sacrifice in mechanical reliability, all the composites fabricated in this study showed a low probability of failure and a factor of safety (~ 5.6) that is consistent with that of human bones (~ 6). In addition, the current study provides an approach to statistically design sintering parameters and mechanical loading for fabrication of ceramics.

Dynamic response of a thin sessile drop of conductive liquid to an abruptly applied or removed electric field.

We consider, both theoretically and experimentally, a thin sessile drop of conductive liquid that rests on the lower plate of a parallel-plate capacitor. We derive analytical expressions for both the initial deformation and the relaxation dynamics of the drop as the electric field is either abruptly applied or abruptly removed, as functions of the geometrical, electrical, and material parameters, and investigate the ranges of validity of these expressions by comparison with full numerical simulations. These expressions provide a reasonable description of the experimentally measured dynamic response of a drop of conductive ionic liquid 1-butyl-3-methyl imidazolium tetrafluoroborate.

Prenatal exposure to allergen, DNA methylation, and allergy in grandoffspring mice.

BACKGROUND: Prenatal allergen exposure has been linked to both induction and protection of allergic sensitization in offspring. We hypothesized that prenatal exposure of mice (F0) to Aspergillus fumigatus (A. fumigatus) would be associated with decreased immunoglobulin (Ig) E and airway eosinophilia and alterations in CpG methylation of T-helper genes in third-generation mice (F2). METHODS: Female BALB/c mice were sensitized to A. fumigatus (62.5, 125, 1250 µg, or saline) and re-exposed to the same dose on days 7 and 14 (early) or days 12 and 17 (late) gestation. Grandoffspring were treated with A. fumigatus (62.5 µg) at 9 weeks. IgE, IgG(1) , and IgG(2a) levels and cell counts from bronchoalveolar lavage fluid were determined. Lung DNA was pyrosequenced at multiple sites in the interferon (IFN)-γ and interleukin (IL)-4 promoters. RESULTS: Grandoffspring of mothers dosed with 1250 µg early during pregnancy developed increased airway eosinophilia (P < 0.05). Grandoffspring of mothers dosed late in pregnancy developed lower IgE (P < 0.05) and airway eosinophilia (P < 0.05). Grandoffspring of mothers dosed early had lower methylation at IL-4 CpG(-408) and CpG(-393) compared to late dosed mice (P < 0.005 across all doses). Few correlations were found between methylation levels and airway eosinophilia and IgE. CONCLUSION: Prenatal exposure to A. fumigatus late during pregnancy, but not early, was associated with lower IgE and airway eosinophilia in grandoffspring. Prenatal exposure to A. fumigatus was associated with changes in CpG methylation in the IFN-γ and IL-4 promoters that did not correlate consistently with indicators of allergic sensitization.

Oxidative stress and iron are implicated in fragmenting vacuoles of Saccharomyces cerevisiae lacking Cu,Zn-superoxide dismutase.

The absence of the antioxidant enzyme Cu,Zn-superoxide dismutase (SOD1) is shown here to cause vacuolar fragmentation in Saccharomyces cerevisiae. Wild-type yeast have 1-3 large vacuoles whereas the sod1Delta yeast have as many as 50 smaller vacuoles. Evidence that this fragmentation is oxygen-mediated includes the findings that aerobically (but not anaerobically) grown sod1Delta yeast exhibit aberrant vacuoles and genetic suppressors of other oxygen-dependent sod1 null phenotypes rescue the vacuole defect. Surprisingly, iron also is implicated in the fragmentation process as iron addition exacerbates the sod1Delta vacuole defect while iron starvation ameliorates it. Because the vacuole is reported to be a site of iron storage and iron reacts avidly with reactive oxygen species to generate toxic side products, we propose that vacuole damage in sod1Delta cells arises from an elevation of iron-mediated oxidation within the vacuole or from elevated pools of "free" iron that may bind nonproductively to vacuolar ligands. Furthermore, additional pleiotropic phenotypes of sod1Delta cells (including increased sensitivity to pH, nutrient deprivation, and metals) may be secondary to vacuolar compromise. Our findings support the hypothesis that oxidative stress alters cellular iron homeostasis which in turn increases oxidative damage. Thus, our findings may have medical relevance as both oxidative stress and alterations in iron homeostasis have been implicated in diverse human disease processes. Our findings suggest that strategies to decrease intracellular iron may significantly reduce oxidatively induced cellular damage.

Variation in the biochemical/biophysical properties of mutant superoxide dismutase 1 enzymes and the rate of disease progression in familial amyotrophic lateral sclerosis kindreds.

Mutations in superoxide dismutase 1 (SOD1) polypeptides cause a form of familial amyotrophic lateral sclerosis (FALS). In different kindreds, harboring different mutations, the duration of illness tends to be similar for a given mutation. For example, patients inheriting a substitution of valine for alanine at position four (A4V) average a 1.5 year life expectancy after the onset of symptoms, whereas patients harboring a substitution of arginine for histidine at position 46 (H46R) average an 18 year life expectancy after disease onset. Here, we examine a number of biochemical and biophysical properties of nine different FALS variants of SOD1 polypeptides, including enzymatic activity (which relates indirectly to the affinity of the enzyme for copper), polypeptide half-life, resistance to proteolytic degradation and solubility, in an effort to determine whether a specific property of these enzymes correlates with clinical progression. We find that although all the mutants tested appear to be soluble, the different mutants show a remarkable degree of variation with respect to activity, polypeptide half-life and resistance to proteolysis. However, these variables do not stratify in a manner that correlates with clinical progression. We conclude that the basis for the different life expectancies of patients in different kindreds of sod1-linked FALS may result from an as yet unidentified property of these mutant enzymes.

Ctf7p is essential for sister chromatid cohesion and links mitotic chromosome structure to the DNA replication machinery.

CTF7 (chromosome transmission fidelity) gene in budding yeast encodes an essential protein that is required for high-fidelity chromosome transmission and contains regions of identity conserved from yeast to man. ctf7 mutant cells arrested prior to anaphase onset contain separated sister chromatids. Thus, Ctf7p is essential for cohesion. Cohesion is established during S phase and then maintained until mitosis. However, Ctf7p activity is required only during S phase, suggesting that Ctf7p functions in the establishment of cohesion. In addition, ctf7 genetically interacts with DNA metabolism mutations pol30 (PCNA) and ctf18 (an RF-C like protein) and ctf7 temperature sensitivity and chromosome loss are rescued by high levels of POL30. These findings provide the first evidence that links the establishment of sister chromatid cohesion to the DNA replication machinery and suggest that the assembly of cohesion (and possibly condensation) complexes are coupled to PCNA-dependent DNA replication. The analysis of Ctf7p also reveals an important connection between sister chromatid cohesion, spindle integrity and the spindle assembly checkpoint.

The copper chaperone CCS is abundant in neurons and astrocytes in human and rodent brain.

Copper trafficking in mammalian cells is highly regulated. CCS is a copper chaperone that donates copper to the antioxidant enzyme copper/zinc superoxide dismutase 1 (SOD 1). Mutations of SOD1 are responsible for approximately 20% of familial amyotrophic lateral sclerosis (FALS). Monospecific antibodies were generated to evaluate the localization and cellular distribution of this copper chaperone in human and mouse brain as well as other organs. CCS is found to be ubiquitously expressed by multiple tissues and is present in particularly high concentrations in kidney and liver. In brain and spinal cord, CCS was found throughout the neuropil, with expression largely confined to neurons and some astrocytes. Like SOD1, CCS immunoreactivity was intense in Purkinje cells, deep cerebellar neurons, and pyramidal cortical neurons, whereas in spinal cord, CCS was highly expressed in motor neurons. In cortical neurons, CCS was present in the soma and proximal dendrites, as well as some axons. Although the distribution of CCS paralleled that of SOD1, there was a 12-30-fold molar excess of SOD1 over CCS. That both SOD1 and CCS are present, together, in cells that degenerate in ALS also emphasizes the potential role of CCS in mutant SOD1-mediated toxicity.

Chaperone-facilitated copper binding is a property common to several classes of familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants.

Mutations in Cu, Zn superoxide dismutase (SOD1) cause the neurodegenerative disease familial amyotrophic lateral sclerosis from an as-yet-unidentified toxic property(ies). Analysis in Saccharomyces cerevisiae of a broad range of human familial amyotrophic lateral sclerosis-linked SOD1 mutants (A4V, G37R, G41D, H46R, H48Q, G85R, G93C, and I113T) reveals one property common to these mutants (including two at residues that coordinate the catalytic copper): Each does indeed bind copper and scavenge oxygen-free radicals in vivo. Neither decreased copper binding nor decreased superoxide scavenging activity is a property shared by all mutants. The demonstration that shows that all mutants tested do bind copper under physiologic conditions supports a mechanism of SOD1 mutant-mediated disease arising from aberrant copper-mediated chemistry catalyzed by less tightly folded (and hence less constrained) mutant enzymes. The mutant enzymes also are shown to acquire the catalytic copper in vivo through the action of CCS, a specific copper chaperone for SOD1, which in turn suggests that a search for inhibitors of this SOD1 copper chaperone may represent a therapeutic avenue.

Experimental arthritis and uveitis in rats associated with Mycobacterium butyricum.

OBJECTIVE: To determine if the anterior uveitis associated with adjuvant arthritis (AA) in the rat can be passively transferred with arthritis to syngeneic recipients using spleen cells or T cell lines prepared from animals given complete Freund's adjuvant (CFA) and Mycobacterium butyricum (M. butyricum) in incomplete Freund's adjuvant (IFA). METHODS: Spleen cells from Lewis or Lewis SsN rats given IFA, CFA, type I collagen in IFA (CI-IFA), or type II collagen in IFA (CII-IFA) were administered to naive rats or rats treated with pertussis toxin or bacterial endotoxin. Three CD4+ T cell lines, propagated from CFA injected rats and maintained in vitro with M. butyricum (M-1), bovine proteoglycan (PR-1) or an extract of M. butyricum (MBE-1) were administered to naive or immunosuppressed rats. The arthritogenic and uveitogenic properties of these cell preparations and intradermal MBE-IFA, CII-IFA and intraperitoneal (ip) M. butyricum without adjuvant were evaluated. RESULTS: Uveitis was observed in 15/69 (22%) arthritic rats given CFA. Spleen cells prepared from CFA injected rats caused arthritis in 55 (82%) and uveitis in 2 (3%) of 67 cell recipients. Uveitis occurred in 2/6 cell recipients pretreated with bacterial endotoxin. Neither uveitis nor arthritis was observed in rats given IFA (0/6) or spleen cells prepared from rats given IFA (0/27), CI-IFA (0/6), or CII-IFA (0/28). CII-IFA produced polyarthritis in 5/6 rats, but no uveitis. CII-IFA induced arthritis associated uveitis in 1/15 animals receiving spleen cells from rats given CII-IFA, but not those given CI-IFA (0/3) or IFA (0/13). Uveitis was observed in one recipient of the M-1 T cell line and in 2 recipients of the PR-1 T cell line. Immunization with 400 micrograms of MBE-IFA induced uveitis but not arthritis in 3/11 animals. The MBE specific T cell line was neither arthritogenic nor uveitogenic. A high frequency (5/6) of uveitis accompanied arthritis in male Lewis rats given ip M. butyricum. Arthritis occurred in 4/10 female Lewis rats given ip M. butyricum and 2 arthritic animals also developed uveitis. CONCLUSION: Uveitis occurs infrequently in arthritic rats given spleen cells from CFA injected animals. The ip administration of M. butyricum constitutes a novel disease model in which the immunopathological relationships between arthritis and uveitis may be more reliably studied.

Relationship between collagen-induced and adjuvant arthritis in the Lewis rat.

Adjuvant arthritis (AA) and type II collagen (CII)-induced arthritis (CIA) in the rat serve as models of chronic human arthritis. Adoptive transfer of AA was observed in 21 of 25 Lewis rats given concanavalin A (Con A)-treated spleen cells prepared from animals immunized with Mycobacterium butyricum in mineral oil (complete Freund's adjuvant, CFA). No arthritic changes were noted in rats given spleen cells obtained from donors that had received incomplete Freund's adjuvant (IFA, 0/22), type I collagen in IFA (CI-IFA, 0/6) or CII-IFA (0/28). Administration of spleen cells from IFA, CI-IFA or CII-IFA-injected animals did not modify the development of CIA when these rats were subsequently challenged with CII-IFA. However, partial protection against induction of AA was provided by the transfer of spleen cells prepared from rats immunized with CII-IFA (6/11) but not by those obtained from rats injected with IFA (1/15) or CI-IFA (0/3). Rats that did not develop clinically evident arthritis following the administration of spleen cells prepared from CFA-injected rats were also resistant to AA induction by CFA. Pre-treatment of rats with a synthetic peptide, corresponding to amino acids 180-188 of the Mycobacterium 65 kD heat shock protein (65 kD HSP), significantly delayed the onset of AA, but not that of CIA. Disease-specific resistance to AA, provided by spleen cells prepared from rats injected with CII-IFA and by pre-treatment with the 65 kD HSP 180-188 peptide, may result from the induction of protective tolerance to arthritogenic epitopes present in the Mycobacterium and CII preparations.