Cathepsin D, the principal indigenous acid proteinase in bovine milk, is a lysosomal proteinase, which exists in milk in four forms, including the inactive zymogen procathepsin D. The thermal ...inactivation kinetics of bovine cathepsin D, isolated from spleen and milk, were studied under isothermal conditions, using a specific HPLC assay to determine residual activity. Inactivation of the blood enzyme preparation followed first order kinetics, with z-values in phosphate buffer (pH 6·7) and skimmed milk of 6·5 and 7·6 °C, respectively, the enzyme being far more stable in the latter environment. Inactivation kinetics of the enzyme purified from milk were more complex, and could be best approximated by a double exponential model. Again, stability was higher in milk than in buffer. The double exponential model may indicate differing heat stabilities of isoforms of the enzyme, or stabilization of the enzyme by some milk constituent. It is clear that the enzyme can survive, at least partially, processes such as heating at 55 °C for 30 min during manufacture of high-cook cheese varieties (45% survival), and HTST pasteurization (8% survival), and thus may contribute to proteolysis in a range of dairy products.
A series of polymethylene-linked 1,8-naphthalimide/viologen diads has been synthesized. The number of intervening methylenes was varied from 2 to 6. For comparison, a series of ...N-alkylpyridiniumyl-1,8-naphthalimide “parent” compounds was prepared and photophysically characterized. Relative to the parent compounds, the electronically excited singlet state of the 1,8-naphthalimide was found to be quenched by the covalently attached viologen. From Stern−Volmer analyses of the steady-state fluorescence spectra, along with the singlet-state lifetime of the pyridinium-substituted 1,8-naphthalimide, the rate constants for intramolecular quenching were calculated to range from 1.5 × 1010 s-1 (2 intervening methylenes) to 8.3 × 107 s-1 (6 intervening methylenes) in aqueous buffered solution. For comparison, the intermolecular reactivity of the excited singlet state of N-alkylpyridiniumyl-1,8-naphthalimides with methylviologen was assessed. In 0.5 M phosphate buffer (pH 7.0), the bimolecular rate constant was found to be 3.2 × 109 M-1 s-1. Nanosecond laser flash photolysis studies were carried out to identify the quenching products. From these studies, reduced methylviologen was identified as a singlet-state quenching product. From these results, we attribute both the intra- and intermolecular quenching process to electron transfer from the singlet excited state of 1,8-naphthalimide to methylviologen. Within the covalently linked series, the rate constant for intramolecular electron transfer was found to vary exponentially with the number of intervening methylenes. Linear least-squares analysis of the results yielded an apparent β value of 1.04 Å-1 for electron transfer through the polymethylene bridge.
We present optical and near-infrared light curves and optical spectra of SN 2013dx, associated with the nearby (redshift 0.145) gamma-ray burst GRB 130702A. The prompt isotropic gamma-ray energy ...released from GRB 130702A is measured to be \(E_{\gamma,iso}=6.4_{-1.0}^{+1.3}\times10^{50}\)erg (1keV-10MeV in the rest frame), placing it intermediate between low-luminosity GRBs like GRB 980425/SN 1998bw and the broader cosmological population. We compare the observed \(g'r'i'z'\) light curves of SN 2013dx to a SN 1998bw template, finding that SN 2013dx evolves ~20% faster (steeper rise time), with a comparable peak luminosity. Spectroscopically, SN 2013dx resembles other broad-lined Type Ic supernovae, both associated with (SN 2006aj and SN 1998bw) and lacking (SN 1997ef, SN 2007I, and SN 2010ah) gamma-ray emission, with photospheric velocities around peak of ~21,000km s\(^{-1}\). We construct a quasi-bolometric (\(g'r'i'z'yJ\)) light curve for SN 2013dx, only the fifth GRB-associated SN with extensive NIR coverage and the third with a bolometric light curve extending beyond \(\Delta t>40\)d. Together with the measured photospheric velocity, we derive basic explosion parameters using simple analytic models. We infer a \(^{56}\)Ni mass of \(M_{\mathrm{Ni}}=0.37\pm0.01\)M\(_{\odot}\), an ejecta mass of \(M_{\mathrm{ej}}=3.1\pm0.1\)M\(_{\odot}\), and a kinetic energy of \(E_{\mathrm{K}}=(8.2\pm0.43)\times10^{51}\) erg (statistical uncertainties only), consistent with previous GRB-associated SNe. When considering the ensemble population of GRB-associated SNe, we find no correlation between the mass of synthesized \(^{56}\)Ni and high-energy properties, despite clear predictions from numerical simulations that \(M_{\mathrm{Ni}}\) should correlate with the degree of asymmetry. On the other hand, \(M_{\mathrm{Ni}}\) clearly correlates with the kinetic energy of the supernova ejecta across a wide range of core-collapse events.
To assess the accuracy of the respiratory inductance plethysmograph (RIP) for monitoring ventilation during sleep-associated bronchoconstriction, five adult patients with nocturnal worsening of their ...asthma were monitored overnight in the sleep laboratory. Three of the five patients demonstrated episodic paradoxic respiratory motion of the lower rib cage undetected by the RIP. Such paradoxic motion was consistently associated with overestimation of volumetric data by RIP compared to pneumotachygraphic measurements. With onset of lower rib cage paradox, the mean error of RIP-derived Vt measurements increased from 9.1 ± 1.7 to 27.9 ± 3.8 percent (p<.001). Flow measurements derived from RIP were also inaccurate in the presence of lower rib cage paradox, with the mean error of the measurement increasing from 9.0 ± 2.5 to 33.5 ± 5.3 percent (p<.001). We conclude that RIP is an unreliable technique for quantitatively monitoring ventilation in sleeping asthmatic patients.
Background Oral immunotherapy (OIT) is an effective experimental food allergy treatment that is limited by treatment withdrawal and the frequent reversibility of desensitization if interrupted. Newly ...diagnosed preschool children may have clinical and immunological characteristics more amenable to treatment. Objective We sought to test the safety, effectiveness, and feasibility of early OIT (E-OIT) in the treatment of peanut allergy. Methods We enrolled 40 children aged 9 to 36 months with suspected or known peanut allergy. Qualifying subjects reacted to peanut during an entry food challenge and were block-randomized 1:1 to receive E-OIT at goal maintenance doses of 300 or 3000 mg/d in a double-blinded fashion. The primary end point, sustained unresponsiveness at 4 weeks after stopping early intervention oral immunotherapy (4-SU), was assessed by double-blinded, placebo-controlled food challenge either upon achieving 4 prespecified criteria, or after 3 maintenance years. Peanut-specific immune responses were serially analyzed. Outcomes were compared with 154 matched standard-care controls. Results Of 40 consented subjects, 3 (7.5%) did not qualify. Overall, 29 of 37 (78%) in the intent-to-treat analysis achieved 4-SU (300-mg arm, 17 of 20 85%; 3000 mg, 12 of 17 71%, P = .43) over a median of 29 months. Per-protocol, the overall proportion achieving 4-SU was 29 of 32 (91%). Peanut-specific IgE levels significantly declined in E-OIT-treated children, who were 19 times more likely to successfully consume dietary peanut than matched standard-care controls, in whom peanut-specific IgE levels significantly increased (relative risk, 19.42; 95% CI, 8.7-43.7; P < .001). Allergic side effects during E-OIT were common but all were mild to moderate. Conclusions At both doses tested, E-OIT had an acceptable safety profile and was highly successful in rapidly suppressing allergic immune responses and achieving safe dietary reintroduction.
Polyphenols are important components of plants, and contribute to colour, aroma and taste, as well as having many other functions. In recent years, considerable research has been conducted on ...polyphenols in foods, focusing on their bioavailability, metabolism and biological effects. This was driven by results of epidemiological studies which showed that diets rich in plant foods are associated with decreased incidence of cancer and heart diseases. Fruits are rich in polyphenols, and the extraction and enrichment of these bioactive compounds from fruit is of increasing academic and commercial interest.
In this review, the numerous approaches that have been investigated and utilised for the enrichment of polyphenols in foods over the last 20 years or so are discussed, mainly focusing on fruit-based products. This review summarises some important aspects of traditional polyphenol enrichment processes such as solvent extraction, as well as reviewing some novel approaches such as the use of colloidal gas aphrons and ohmic heating. Applications of each process are explained, advantages and disadvantages discussed, and recovery and enrichment levels of polyphenols presented.
Key findings and conclusions: Pre-treatments such as enzymatic hydrolysis, pulsed electric fields and high-pressure processing can be applied to fruit-based products to improve polyphenol extraction efficiency. There is high potential for the use of environmentally friendly processes for enrichment of polyphenols from fruit-based products using membrane filtration. Polyphenol enrichment technologies need to be cost-effective and rapid and facilitate retention of the biological activities of the polyphenols.
•Recovery of polyphenols is widely researched due to their potential applications.•The food industry requires clean and cost-effective polyphenol enrichment processes.•Membrane technology and pressurised liquid extraction are potentially exciting.•Solvent extraction has poor selectivity and generates solvent waste streams.•Pre-treatments, e.g., ohmic heating, can be used to improve extraction efficiency.
Flow cytometry of classical neuroblastoma has provided provocative evidence that cell cycle and ploidy analysis generate prognostically useful information. To determine whether such analyses of ...peripheral primitive neuroectodermal tumors might yield similar results, formalin-fixed, paraffin-embedded tissue specimens from 19 peripheral primitive neuroectodermal tumors, each previously characterized by immunohistochemical or ultrastructural study, were assessed. An acceptable histogram was obtained in 16 cases. Of these, nine neoplasms were diploid and seven contained aneuploid DNA. Among patients with diploid lesions, four were free of disease, whereas three had persistent or recurrent disease, and two had died of tumor. Among patients with aneuploid neoplasms, four were free of disease, one had recurrence, and two had died. There was no apparent correlation between immunophenotype and proliferative activity with the clinical outcome. Among aneuploid peripheral primitive neuroectodermal tumors, DNA index did not predict survival. Hence, cell cycle and DNA ploidy analyses do not appear to contribute to the prognostic assessment of peripheral primitive neuroectodermal tumors, as they do to presumably related neoplasms of the central and peripheral nervous system.