Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with ...increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients.
In the article, a method is developed for estimating the dynamic masses of the stellar and gas components of cluster-cloud systems under conditions of non-isolation and significant non-stationarity ...of stellar and gas subsystems in a regular field. A number of estimates of the dynamic masses of the stellar and gas components of the system are made without using the virial theorem for zero and positive values of the total energies
of the system as a whole and
of its gaseous subsystem. The well-known estimates of the free-fall time
for fragments in the force field of a sphere of uniform and inhomogeneous density sphere simulating a system of gas and stars are refined. The estimates of the
quantities are supplemented by estimates of the radial velocities
of the fragments in such systems. A number of relations between the parameters of the stellar and gas subsystems in the considered models of embedded clusters are obtained. It is shown that instead of one virial coefficient to describe the system, it is necessary to use three coefficients, the formulas for which are given. The relations make it possible to estimate the dynamic masses of non-isolated and non-stationary subsystems from data on the structural-dynamic characteristics of an embedded cluster. It is shown that the ratio
, where
is the mean square of the velocities of the stellar subsystem in the case of its virial equilibrium, and
is the mean square of the critical velocities of the stars in this subsystem. It is shown that embedded clusters with parameters
and
have maximum values
along some curve in the
space (
and
are the mass and radius of the
th subsystem). The embedded clusters with parameters
close to this curve are the least susceptible to destruction space relaxation processes. It is shown that, depending on the initial energies
and
, the masses of a subsystem of stars in an embedded cluster can be much smaller than the virial masses of this subsystem. This result is also of particular interest for estimating the dynamic masses of galaxy clusters. It is noted that an increase in the degree of non-stationarity of the considered models of embedded clusters leads to a decrease in the periods of oscillations of the stellar subsystem.
Angiotensin-converting enzyme (ACE) metabolizes a number of important peptides participating in blood pressure regulation and vascular remodeling. Elevated ACE expression in tissues (which is ...generally reflected by blood ACE levels) is associated with an increased risk of cardiovascular diseases. Elevated blood ACE is also a marker for granulomatous diseases. Decreased blood ACE activity is becoming a new risk factor for Alzheimer's disease. We applied our novel approach-ACE phenotyping-to characterize pairs of tissues (lung, heart, lymph nodes) and serum ACE in 50 patients. ACE phenotyping includes (1) measurement of ACE activity with two substrates (ZPHL and HHL); (2) calculation of the ratio of hydrolysis of these substrates (ZPHL/HHL ratio); (3) determination of ACE immunoreactive protein levels using mAbs to ACE; and (4) ACE conformation with a set of mAbs to ACE. The ACE phenotyping approach in screening format with special attention to outliers, combined with analysis of sequencing data, allowed us to identify patient with a unique ACE phenotype related to decreased ability of inhibition of ACE activity by albumin, likely due to competition with high CCL18 in this patient for binding to ACE. We also confirmed recently discovered gender differences in sialylation of some glycosylation sites of ACE. ACE phenotyping is a promising new approach for the identification of ACE phenotype outliers with potential clinical significance, making it useful for screening in a personalized medicine approach.
We hypothesized that subjects with heterozygous loss-of-function (LoF)
mutations are at risk for Alzheimer's disease because amyloid Aβ42, a primary component of the protein aggregates that ...accumulate in the brains of AD patients, is cleaved by ACE (angiotensin I-converting enzyme). Thus, decreased ACE activity in the brain, either due to genetic mutation or the effects of ACE inhibitors, could be a risk factor for AD. To explore this hypothesis in the current study, existing SNP databases were analyzed for LoF
mutations using four predicting tools, including PolyPhen-2, and compared with the topology of known
mutations already associated with AD. The combined frequency of >400 of these LoF-damaging
mutations in the general population is quite significant-up to 5%-comparable to the frequency of AD in the population > 70 y.o., which indicates that the contribution of low ACE in the development of AD could be under appreciated. Our analysis suggests several mechanisms by which ACE mutations may be associated with Alzheimer's disease. Systematic analysis of blood ACE levels in patients with all
mutations is likely to have clinical significance because available sequencing data will help detect persons with increased risk of late-onset Alzheimer's disease. Patients with transport-deficient
mutations (about 20% of damaging ACE mutations) may benefit from preventive or therapeutic treatment with a combination of chemical and pharmacological (e.g., centrally acting ACE inhibitors) chaperones and proteosome inhibitors to restore impaired surface ACE expression, as was shown previously by our group for another transport-deficient ACE mutation-Q1069R.
The situation evolved in the domain of fuel additives production during 2011-2015 is reviewed through the analysis of literature and patent sources and statistical data. The main trends in ...development of additives are determined and the main types of additives are characterized. It is noted that the interest of developers worldwide was focused on additives of biocomponents (oxygenates and biodiesel). In Russia, where imported additives were prevalent until recently, active process of import substitution has begun. The additive demand of Russian refineries for the production of modern quality fuels is analyzed and the domestic developments are characterized. Technical solutions that offer alternatives to the use of additives are proposed.
This paper presents a comparative analysis of electrochromic properties of nonstoichiometric hydrated films CuWO
3.7
·2H
2
O, WO
2.5
·2H
2
O, and α-WO
2.9
·H
2
O obtained by combined electrochemical ...and chemical methods. The use of EDAX X-ray diffraction and UV VIS spectroscopy and the Smacula-Dexter equation helped to determine that of differences in spectral and electrochemical characteristics CuWO
3.7
·2H
2
O, WO
2.5
·2H
2
O, and α-WO
2.9
·H
2
O electrochromic process as results chemical composition, stoichiometry, and the structure films based on W oxide compounds, where the contribution to the electrochromic film coloration is mainly done using localized states of W
5+
, W
4+
, and additionally Cu
+
in the case of CuWO
3.7
·2H
2
O. This allows CuWO
3.7
·2H
2
O extending light absorption at the electrochromic coloration in the 450–650 nm visible region spectrum. At the same time, diffusion processes are slowed down due to the complementary electrochromic coloration of copper oxide compounds, which reduces the rate and efficiency CuWO
3.7
·2H
2
O film compared to WO
2.5
·2H
2
O and α-WO
2.9
·H
2
O. This helped to establish that the metal tungstates can be effective electrochromic material as is WO
3
with an additional absorption band provided that the dimensionally diffusion rates of protons or lithium ions in both oxide components are achieved.
Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in reproductive functions, is expressed as a ...type-1 membrane glycoprotein on the surface of endothelial and epithelial cells. ACE also presents as a soluble form in biological fluids, among which seminal fluid being the richest in ACE content - 50-fold more than that in blood.
We performed conformational fingerprinting of lung and seminal fluid ACEs using a set of monoclonal antibodies (mAbs) to 17 epitopes of human ACE and determined the effects of potential ACE-binding partners on mAbs binding to these two different ACEs. Patterns of mAbs binding to ACEs from lung and from seminal fluid dramatically differed, which reflects difference in the local conformations of these ACEs, likely due to different patterns of ACE glycosylation in the lung endothelial cells and epithelial cells of epididymis/prostate (source of seminal fluid ACE), confirmed by mass-spectrometry of ACEs tryptic digests.
Dramatic differences in the local conformations of seminal fluid and lung ACEs, as well as the effects of ACE-binding partners on mAbs binding to these ACEs, suggest different regulation of ACE functions and shedding from epithelial cells in epididymis and prostate and endothelial cells of lung capillaries. The differences in local conformation of ACE could be the base for the generation of mAbs distingushing tissue-specific ACEs.
Aviation products exhibit certain distinctive features. In particular, they must meet strict requirements on the dimensional precision and surface roughness. In addition, they are produced from ...special materials. Thin-walled shells are often encountered. The housing of an aircraft engine is a good example. In turning such casings, the whole profile must be machined in a single pass, so as to ensure the specified surface roughness. In machining the thin-walled workpiece, dimensional errors arise. That may result in expensive losses of flawed workpieces or at least requires laborious additional machining. In the present work, an approach is proposed for automatically decreasing the error, without additional operations.
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