The degradation of klerval (
I) was studied as a function of pH. The extent and routes of degradation were found to be pH-dependent. Under strongly acidic conditions (pH<2), the drug predominantly ...undergoes specific acid-catalyzed hydrolysis of the side-chain amide bond yielding
II. In weakly acidic solutions (2<pH<4), the backbone amide bond was found to be hydrolyzed forming a tripeptide. The cleavage reaction proceeds via intramolecular catalysis by carboxyl group displacement of the nitrogen of the peptide bond. In addition, parallel formation of a small amount of succinimide was observed in acidic solutions (1<pH<5). In neutral solutions (5<pH<8), the peptide isomerizes via the succinimide producing the iso-aspartyl isomer. The isomerization was found to be pH-independent throughout neutral and basic pH regions. In basic solutions (pH>8), the drug undergoes specific base-catalyzed hyrolysis yielding
II and epimerization generating
d-epimer. The epimerization appears to occur via the succinimide intermediate in neutral pH region. With increasing pH, however, the epimerization rate increases due to direct epimerization of the peptides.
A cross-sectional study of spinal stereoradiographs of adolescents with scoliosis to measure growth.
To determine the relative contributions of the vertebral bodies and intervertebral discs to the ...increase in spinal length between T5 and L5, over the age range of 7.5-20 years.
The progression of spinal deformity (scoliosis) is associated with skeletal growth, but the relative roles of asymmetrical growth and remodeling of the vertebrae and discs during adolescent growth are unclear.
An existing database of 406 spinal stereoradiographic studies of 188 adolescents with idiopathic scoliosis, aged between 7.5 and 20 years, was used to measure the heights of vertebral bodies and intervertebral discs, and the summation of both (spinal length).
Spinal length was observed to increase from about 250 to 350 mm over this range of ages. Spinal growth was associated with an increase in vertebral height after age 10 years, with minimal if any increase in disc height. The contribution of vertebral and discal height was estimated to be about 17 and 8 mm per year, respectively, at age 7.5 years, but discal height growth was estimated to be effectively zero after age 12 years.
Spinal growth of patients with scoliosis aged between 10 and 20 years occurs almost exclusively by height increases in the vertebrae, not the discs.
How B2B firms in the People's Republic of China PRC view, value and manage their corporate reputation has received little research attention. Drawing on multiple case studies, our findings confirm ...that firms are utilizing certain Western conceptualizations of corporate reputation, including the leveraging of intangible forms of corporate reputation. However, many of the firms were also using the hitherto underemphasized elements of firm–government relationships and government regulatory policies to create positive assessments of a firm's reputation among key stakeholders. Notwithstanding our findings that corporate reputation is valued as a means of gaining competitive advantage and dispelling perceptions that Chinese products/services are low-cost and low-quality, concern remains that building reputation capital among stakeholders may result in a loss of price competitiveness. Finally, unlike the framework proposed by Barnett, Jermier, and Lafferty (2006), our results suggest that B2B firms in China do not impose clear boundaries between reputation and ‘corporate reputation capital’. Nor does there appear to be an emphasis on disaggregating the constructs of identify and image from that of reputation.
Protein tyrosine kinase (PTK) activities in methyl nitrosourea (MNU)-induced rat mammary carcinoma has been investigated by using poly (glu: tyr; 4:1) as an exogenous substrate. The PTK activity of ...the mammary carcinoma was almost equally distributed between the particulate and soluble (cytosolic) fractions at 110,000 X g. The activity of the particulate enzyme was stimulated by non-ionic detergent Triton X-100 by about 2-fold whereas the detergent had no effect on the cytosolic form. More than 60% of the particulate enzyme could be solubilized by 5% Triton X-100. Although, both particulate and cytosolic PTKs catalyzed the phosphorylation of several tyrosine containing synthetic substrates to various degrees, poly (glu: tyr; 4:1) was the best substrate (apparent Km. 0.7 mg/ml). Both forms of enzymes utilized ATP as the phosphoryl group donor, with an apparent Km of 40 microM. Among various divalent cations tested, Co2+, Mn2+ and Mg2+ were able to fulfill the divalent cation requirement of both forms of the PTKs. All these cations exerted biphasic effects on the kinase activities, however, Mg2+ was the most potent cation. Agents such as epidermal growth factor, insulin and platelet derived growth factor which stimulate their respective receptor-PTK activities were without effect on PTK activities of mammary carcinoma. On the other hand, though heparin and quercetin inhibited both enzyme activities in a concentration dependent manner, the particulate form was more sensitive to inhibition than the cytosolic form. These data indicate that MNU-induced rat mammary carcinoma expresses both particulate and cytosolic forms of PTKs and that there are significant differences in the properties of the two forms of PTKs. Differential effects of some agents on mammary carcinoma PTKs suggest that these enzymes may be acutely regulated in vivo and could play an important role in mammary carcinogenesis.
Controlling growth: Large arrays of oriented conducting polymer nanowires were prepared by controlled nucleation and growth during a stepwise electrochemical deposition process, without the use of ...porous membrane supports (see scheme and electron micrographs).
The optimized, superconducting stellarator Wendelstein 7-X went into operation and delivered first measurement data after 15 years of construction and one year commissioning. Errors in the magnet ...assembly were confirmend to be small. Plasma operation was started with 5 MW electron cyclotron resonance heating (ECRH) power and five inboard limiters. Core plasma values of Te>8 keV, Ti>2 keV at line-integrated densities n≈3⋅1019 m−2 were achieved, exceeding the original expectations by about a factor of two. Indications for a core-electron-root were found. The energy confinement times are in line with the international stellarator scaling, despite unfavourable wall conditions, i.e. large areas of metal surfaces and particle sources from the limiter close to the plasma volume. Well controlled shorter hydrogen discharges at higher power (4 MW ECRH power for 1 s) and longer discharges at lower power (0.7 MW ECRH power for 6 s) could be routinely established after proper wall conditioning. The fairly large set of diagnostic systems running in the end of the 10 weeks operation campaign provided first insights into expected and unexpected physics of optimized stellarators.
The dissolution kinetics of five glasses along the NaAlSiO
4–NaBSiO
4 join were used to evaluate how the structural variations associated with boron–aluminum substitution affect the rate of ...dissolution. The composition of each glass varied inversely in mol% of Al
2O
3 (5–25
mol%) and B
2O
3 (20–0
mol%) with Na
2O (25
mol%) and SiO
2 (50
mol%) making up the remaining amount, in every case Na/(Al
+
B)
=
1.0. Single-pass flow-through experiments (SPFT) were conducted under dilute conditions as a function of solution pH (from 7.0 to 12.0) and temperature (from 23 to 90
°C). Analysis of unreacted glass samples by
27Al and
29Si MAS-NMR suggests Al (∼98%
4Al) and Si-atoms (∼100%
4Si) occupy a tetrahedral coordination whereas, B-atoms occupy both tetrahedral (
4B) and trigonal (
3B) coordination. The distribution of
3B fractionated between
3B(ring) and
3B(non-ring) moieties, with the
3B(ring)/
3B(non-ring) ratio increases with an increase in the B/Al ratio. The MAS-NMR results also indicated an increase in the fraction of
4B with an increase in the B/Al ratio. The
27Al peak maxima shift to lesser values with an increase in the B/Al ratio which suggests mixing between the
4Al and
3B sites, assuming avoidance between tetrahedral trivalent cations (
4Al–O–
4B avoidance). Unlike the
27Al and
11B spectra, the
29Si spectra illustrate a subtle shift to more negative chemical shift (chemical shift range between −88 and −84
ppm) and increases in the spectral widths as the B/Al ratio increases. Raman spectroscopy of unreacted glass samples was also used to cross-check the results collected from MAS-NMR and suggested that NeB4 (the glass sample with the highest B content) may consist of B–Na enriched and Al–Si enriched micro-domains, which affected the measured dissolution rates. Results from SPFT experiments suggest a forward rate of reaction and pH power-law coefficients,
η, that are independent of B/Al under these neutral to alkaline test conditions for all homogeneous glasses. The temperature dependence shows an order of magnitude increase in the dissolution rate with a 67
°C increase in temperature and suggests dissolution is controlled by a surface-mediated reaction, as indicated by the activation energy,
E
a
, being between 44
±
8 and 48
±
7
kJ/mol. Forward dissolution rates, based on Na and Si release, for homogeneous glasses are independent of the B/Al ratio, whereas dissolution rates based on Al and B release are not. Normalized dissolution rates, based on B release, increase with the molar fraction of
3B(ring). Finally in accord with previous studies, the data discussed in this manuscript suggest rupture of either the Al–O or Si–O bonds as the rate-limiting step controlling the dissolution of these glasses.
Vitamin D supplementation has been suggested to enhance immunity during respiratory infection season. We tested the effect of active vitamin D (calcitriol) supplementation on key airway innate immune ...mechanisms in vitro.
Primary human airway epithelial cells (hAECs) grown at the air liquid interface were supplemented with 10-7 M calcitriol for 24 hours (or a time course) and their antimicrobial airway surface liquid (ASL) was tested for pH, viscoscity, and antibacterial and antiviral properties. We also tested hAEC ciliary beat frequency (CBF). Next, we assessed alterations to hAEC gene expression using RNA sequencing, and based on results, we measured neutrophil migration across hAECs.
Calcitriol supplementation enhanced ASL bacterial killing of Staphylococcus aureus (p = 0.02) but did not enhance its antiviral activity against 229E-CoV. It had no effect on ASL pH or viscosity at three timepoints. Lastly, it did not affect hAEC CBF or neutrophil migration, although there was a trend of enhanced migration in the presence of a neutrophil chemokine (p = 0.09). Supplementation significantly altered hAEC gene expression, primarily of AMP-related genes including CAMP and TREM1.
While vitamin D supplementation did not have effects on many airway innate immune mechanisms, it may provide a useful tool to resolve respiratory bacterial infections.
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