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Spatial contaminant heterogeneity: quantification with scale of measurement at contrasting sites.

Material within the terrestrial environment is rarely homogeneously distributed, either spatially or temporally. One consequence of heterogeneity is that uncertainty is usually generated in measurements that are taken with the aim of characterising the environment. For example, a measurement of analyte concentration within soil taken from one sampling location on contaminated land can vary substantially when compared against another sample taken at effectively the same nominal location. The measurement uncertainty arising from the heterogeneity can substantially limit the reliability of the interpretations made upon environmental investigations. The sampling uncertainty usually outweighs the analytical uncertainty from the laboratory, often by a factor of 20 or more. One approach to reducing the uncertainty is to design a more suitable sampling strategy. This might be achieved by predicting the degree of heterogeneity prior to the investigation, but this is often difficult to achieve accurately. Another approach, which was investigated here, is to actually characterise the heterogeneity prior to the main investigation using rapid and inexpensive technology, such as in situ measurement techniques. In situ portable X-ray fluorescence (PXRF) and X-ray microprobe (XMP) techniques were employed to test the feasibility of this approach. Two contrasting contaminated land sites were chosen to characterise the two-dimensional spatial heterogeneity of heavy metal contamination in topsoil at a range of scales (50 m to 0.001 m). The spatial heterogeneity of contaminants, expressed as relative standard deviations, was found to differ between the two sites by a factor of two, largely due to the mode of deposition of pollution. The study also indicated that the heterogeneity did not change systematically with the scale of measurement between sampling locations at either site.

England↗

Influence of genetic factors on the magnitude and the heterogeneity of the immune response in the rabbit.

Selective breeding of rabbits immunized with Group C and Group A streptococcal vaccines was employed to reveal genetic influences on the magnitude and on the restriction in heterogeneity of the immune response to the group-specific carbohydrates. After two generations of selective breeding, complete segregation was achieved between a high-response population (>18 mg precipitins/ml serum, average 33 mg/ml) and a low-response population (<13 mg precipitins/ml serum, average 7.5 mg/ml) to Group C carbohydrate. This suggests that a limited number of genes controls the magnitude of the immune response to this antigen. Selective breeding of rabbits which were representative of heterogeneous, restricted, and monoclonal responses revealed that the degree of antibody heterogeneity in the parental rabbits is reflected in the offspring. More than 95% of the offspring derived from rabbits which had a heterogeneous immune response developed heterogeneous antibodies. 33% of the offspring derived from rabbits which had restricted and monoclonal immune responses developed monoclonal antibodies. This suggests that the degree of heterogeneity of the antibody response to the streptococcal carbohydrates is under genetic control. The degree of heterogeneity and the magnitude of the immune response appear to be independent variables.

Animals↗

Nutrient availability and atmospheric CO2 partial pressure modulate the effects of nutrient heterogeneity on the size structure of populations in grassland species.

BACKGROUND AND AIMS: Size-asymmetric competition occurs when larger plants have a disproportionate advantage in competition with smaller plants. It has been hypothesized that nutrient heterogeneity may promote it. Experiments testing this hypothesis are inconclusive, and in most cases have evaluated the effects of nutrient heterogeneity separately from other environmental factors. The aim of this study was to test, using populations of Lolium perenne, Plantago lanceolata and Holcus lanatus, two hypotheses: (a) nutrient heterogeneity promotes size-asymmetric competition; and (b) nutrient heterogeneity interacts with both atmospheric CO2 partial pressure (P(CO2)) and nutrient availability to determine the magnitude of this response. METHODS: Microcosms consisting of monocultures of the three species were grown for 90 d in a factorial experiment with the following treatments: P(CO2) (37.5 and 70 Pa) and nutrient availability (NA; 40 and 120 mg of N added as organic material) combined with different spatial distribution of the organic material (NH; homogeneous and heterogeneous). Differences in the size of individual plants within populations (size inequality) were quantified using the coefficient of variation of individual above-ground biomass and the combined biomass of the two largest individuals in each microcosm. Increases in size inequality were associated with size-asymmetric competition. KEY RESULTS: Size inequality increased when the nutrients were heterogeneously supplied in the three species. The effects of NH on this response were more pronounced under high nutrient supply in both Plantago and Holcus (significant NA x NH interactions) and under elevated P(CO2) in Plantago (significant P(CO2) x NA x NH interaction). No significant two- and three-way interactions were found for Lolium. CONCLUSIONS: Our first hypothesis was supported by our results, as nutrient heterogeneity promoted size-asymmetric competition in the three species evaluated. Nutrient supply and P(CO2) modified the magnitude of this effect in Plantago and Holcus, but not in Lolium. Thus, our second hypothesis was partially supported.

Atmospheric Pressure↗

Is there any physiological role for gonadotrophin oligosaccharide heterogeneity in humans? II. A biochemical point of view.

Heterogeneity of gonadotrophin oligosaccharides caused either by pharmacological intervention or which occurs naturally during normal physiological changes is well documented. Recent advances in structure determination of oligosaccharides has to some extent led to a better appreciation of how oligosaccharide heterogeneity may affect protein folding, stability, measurement and modulation of receptor binding. Here it is discussed how carbohydrate structure can impact upon gonadotrophin structure and function. It is well documented that oligosaccharides can serve as a cognate site for protein binding. One functional aspect of gonadotrophin glycosylation heterogeneity is the modulation of receptor binding affinity, yielding partially agonistic glycoforms. Carbohydrate heterogeneity is problematic for a clinical chemist if immunochemical assays are sensitive to heterogeneity. However, even measurements made without such interference may not accurately reflect the biological activity that is a collective result of all isoforms in the circulation, and perhaps of the genotype of each individual. Moreover, oligosaccharide heterogeneity may affect heterodimer stability, therefore, biological activity and immunochemical activity, not to mention clearance. It seems reasonable to conclude that from a biochemical point of view, oligosaccharide heterogeneity is of considerable importance. However, accurate measurement of isoforms in blood, and appropriate in-vitro bioassays that are insensitive to matrix effects are needed to define the physiological significance of each glycoform, and thereby better define target therapeutics and interpret diagnostic results.

Binding Sites↗

Marked intratumoral heterogeneity of c-myc and cyclinD1 but not of c-erbB2 amplification in breast cancer.

Intratumoral heterogeneity mirrors subclonal diversity and might affect treatment response. To investigate molecular heterogeneity of primary breast cancer specimens, we determined the amplification status of growth regulatory genes (c-erbB2, topoisomerase IIalpha, c-myc, and cyclinD1) in macroscopically and microscopically separate areas of individual tumors (n = 21). Using laser-assisted microdissection and quantitative PCR, we found marked intratumoral heterogeneity with different patterns for each gene. Molecular heterogeneity in amplification pattern could be demonstrated between both macroscopically (0.5 to several centimeters) and microscopically (10 to several hundred micrometers) distant tumor areas. C-erbB2 amplification proved to be the most stable amplification in individual tumors, with heterogeneity occurring in only 36% of amplified cases. By contrast, amplification of c-myc and cyclinD1 revealed varying patterns in the vast majority of amplified cases (100% and 83%). The constancy of c-erbB2 amplification underlines its presumed importance in breast cancer biology. We conclude that the molecular heterogeneity of breast cancer as evidenced in this study requires thorough and representative sampling of different tumor areas when the biologic significance of somatic mutations is considered. Patterns of heterogeneity can be used to trace the clonal evolution within different compartments of an individual tumor.

Breast Neoplasms↗

Heterogeneity of cerebral blood flow in symptomatic patients undergoing carotid endarterectomy.

There is still controversy concerning which patients with asymptomatic carotid stenosis or symptomatic moderate stenosis are likely to benefit from carotid endarterectomy. The surgical candidates for carotid endarterectomy should have a high risk for stroke, but a low risk for operative complications. Therefore, new effective patient selection strategies, including haemodynamic testing, schemes of risk stratification and pre-operative cardiac testing, are under investigation. To improve haemodynamic assessment of patients with carotid artery stenosis, we evaluated a novel global cerebral blood flow (CBF) heterogeneity index at rest and after acetazolamide injection in patients undergoing carotid endarterectomy. CBF heterogeneity index was measured in 15 patients by using basal and acetazolamide enhanced 99mTc-HMPAO SPET both before and 1 month after surgery. CBF heterogeneity index was calculated as the coefficient of variation of a total of 44 cerebral regions representing mainly both ipsi- and contralateral grey matter. A high linear correlation was observed between CBF heterogeneity index and ipsilateral carotid stenosis degree (r=0.74, P=0.003). Before surgery, CBF heterogeneity index increased significantly after acetazolamide injection when compared to the basal condition (from 7.0+/-1.5 to 8.3+/-1.7%, P=0.008). This response disappeared after carotid endarterectomy. When compared to pure asymmetry of CBF (ipsi/contralateral CBF ratio), the CBF heterogeneity index seemed to reflect, more sensitively, the haemodynamic effects of carotid endarterectomy. The CBF heterogeneity index after acetazolamide injection is a sensitive marker of the haemodynamic consequences of carotid artery stenosis and its operative treatment.

Acetazolamide↗

Index for spatial heterogeneity in breast cancer.

Histopathological heterogeneity in cancer is a general concern. Breast carcinoma heterogeneity is now widely admitted as a source of histological grading imprecision and reproducibility problems. Classically, homogeneity is defined as equivalent to stationarity. A measure of heterogeneity based on asymptotic properties of spatial statistics is developed. Long-range dependences in heterogeneous spatial processes make estimation of the proposed heterogeneity measure unreliable. A robust estimator based on the wavelet transform is presented; this bypasses long-range dependences. The estimator extends previous works on one-dimensional stochastic processes to two dimensions as appropriate for histopathological analysis. As a side result, the estimator gives confidence intervals for the heterogeneity measure that enables the formulation and validation of testable hypothesis on the observed histopathological samples. This approach is applied to the characterization of breast cancer tumours. We show that the heterogeneity measure for various blocks of a single tumour is invariable, even when various blocks differ in size and in number of marked nuclei.

Breast Neoplasms↗

Phenotypic heterogeneity can enhance rare-cell survival in 'stress-sensitive' yeast populations.

Individual cells within isogenic microbial cultures exhibit phenotypic heterogeneity, an issue that is attracting intense interest. Heterogeneity could confer benefits, in generating variant subpopulations that may be better equipped to persist during perturbation. We tested this hypothesis by comparing the survival of wild-type Saccharomyces cerevisiae with that of mutants which are considered stress-sensitive but which, we demonstrate, also have increased heterogeneity. The mutants (e.g. vma3, ctr1, sod1) exhibited the anticipated sensitivities to intermediate doses of nickel, copper, alkaline pH, menadione or paraquat. However, enhanced heterogeneity meant that the resistances of individual mutant cells spanned a broad range, and at high stress occasional-cell survival in most of these populations overtook that of the wild type. Green fluorescent protein (GFP) reporter studies showed that this heterogeneity-dependent advantage was not related to perturbation of buffered gene expression. Deletion strain screens combined with other approaches revealed that vacuolar alkalinization resulting from loss of Vma-dependent vacuolar H(+)-ATPase activity was not the cause of vma mutants' net stress sensitivities. An alternative Vma-dependent resistance mechanism was found to suppress an influence of variable vacuolar pH on the metal resistances of individual wild-type cells. In addition to revealing new mechanisms of heterogeneity generation, the results demonstrate experimentally a benefit under adverse conditions that arises specifically from heterogeneity, and in populations conventionally considered to be disadvantaged.

Acids↗

Invasion in a heterogeneous world: resistance, coexistence or hostile takeover?

We review and synthesize recent developments in the study of the invasion of communities in heterogeneous environments, considering both the invasibility of the community and impacts to the community. We consider both empirical and theoretical studies. For each of three major kinds of environmental heterogeneity (temporal, spatial and invader-driven), we find evidence that heterogeneity is critical to the invasibility of the community, the rate of spread, and the impacts on the community following invasion. We propose an environmental heterogeneity hypothesis of invasions, whereby heterogeneity both increases invasion success and reduces the impact to native species in the community, because it promotes invasion and coexistence mechanisms that are not possible in homogeneous environments. This hypothesis could help to explain recent findings that diversity is often increased as a result of biological invasions. It could also explain the scale dependence of the diversity-invasibility relationship. Despite the undoubted importance of heterogeneity to the invasion of communities, it has been studied remarkably little and new research is needed that simultaneously considers invasion, environmental heterogeneity and community characteristics. As a young field, there is an unrivalled opportunity for theoreticians and experimenters to work together to build a tractable theory informed by data.

Animals↗

Heterogeneity of splanchnic vascular transit times in man.

A new method of quantifying the heterogeneity of transit times through vascular beds, free from corrections for effects of recirculation, is applied to data of splanchnic transit times in eight normal subjects and three patients with cirrhosis and end-to-side portocaval shunts, as obtained by Bradley's method. There is proportionality between the heterogeneity, expressed as standard deviation and the mean transit time in the eight normal subjects. The heterogeneity of plasma transit times is not appreciably larger than that of red blood cells, despite the larger volume of distribution of plasma. This may suggest that the large vessels contribute substantially to the dispersions of vascular transits in the entire splanchnic system. Pearson Type III distribution is proposed for the frequency function of the splanchnic transit times, and the power of the pre-exponential factor is deduced for plasma and for red blood cells. It is found that the initial splanchnic transits are dominated by plasma, this may be due to sequestration of red cells in the spleen. The heterogeneity of transit times in normals is not appreciably different from that in patients with cirrhosis and portocaval shunt, which suggests that the extra heterogeneity of the cirrhotic liver is of the same order as the heterogeneity of the normal extrahepatic splanchnic organs. The method may be a useful tool to describe heterogeneity of vascular transits in other organs.

Adolescent↗

Spatial weighting functions: transient hydraulic tests and heterogeneous media.

To improve understanding of property measurements in heterogeneous media, an energy-based weighting function concept is developed. In (assumed) homogeneous media, the instrument spatial weighting function (ISWF) depends only on the energy dissipation distribution set up by the measurement procedure and it reduces to simply inverse sample volume (uniform weighting) for 1-D parallel flow case (ideal permeameter). For 1-D transient flow in homogeneous media, such as with slug tests, the ISWF varies with position and time, with 95% of the total weighting contained within 115 well radii, even late in the test. In the heterogeneous case, the determination of the ISWF is connected to the problem of determining an equivalent hydraulic conductivity (K), where the criterion for equivalence is based on equal energy dissipation rate rather than equal volume discharge. The discharge-based equivalent K (K(E)) and the energy-based equivalent K in heterogeneous media (K(eh)) are not equal in general, with K(eh) typically above the nodal arithmetic mean K. The possibly more fundamental problem is that as one makes K measurements in heterogeneous media at different locations or on different cores of heterogeneous materials, the ISWF will be heterogeneity dependent, implying that the averaging process resulting in the equivalent K value also varies with position. If the testing procedure is transient, then the averaging process varies with time. This suggests a fundamental ambiguity in the interpretation of hydraulic conductivity measurements in heterogeneous media that may impact how we approach modeling and prediction in a practical sense (Molz 2003). Further research is suggested.

Models, Theoretical↗

Estimation of blood flow heterogeneity in human skeletal muscle using intravascular tracer data: importance for modeling transcapillary exchange.

Distributed models of blood-tissue exchange are widely used to measure kinetic events of various solutes from multiple tracer dilution experiments. Their use requires, however, a careful description of blood flow heterogeneity along the capillary bed. Since they have mostly been applied in animal studies, direct measurement of the heterogeneity distribution was possible, e.g., with the invasive microsphere method. Here we apply distributed modeling to a dual tracer experiment in humans, performed using an intravascular (indocyanine green dye, subject to distribution along the vascular tree and confined to the capillary bed) and an extracellular ([3H]-D-mannitol, tracing passive transcapillary transfer across the capillary membrane in the interstitial fluid) tracer. The goal is to measure relevant parameters of transcapillary exchange in human skeletal muscle. We show that assuming an accurate description of blood flow heterogeneity is crucial for modeling, and in particular that assuming for skeletal muscle the well-studied cardiac muscle blood flow heterogeneity is inappropriate. The same reason prevents the use of the common method of estimating the input function of the distributed model via deconvolution, which assumes a known blood flow heterogeneity, either defined from literature or measured, when possible. We present a novel approach for the estimation of blood flow heterogeneity in each individual from the intravascular tracer data. When this newly estimated blood flow heterogeneity is used, a more satisfactory model fit is obtained and it is possible to reliably measure parameters of capillary membrane permeability-surface product and interstitial fluid volume describing transcapillary transfer in vivo.

Blood Flow Velocity↗

Two distinct mechanisms cause heterogeneity of 16S rRNA.

To investigate the frequency of heterogeneity among the multiple 16S rRNA genes within a single microorganism, we determined directly the 120-bp nucleotide sequences containing the hypervariable alpha region of the 16S rRNA gene from 475 Streptomyces strains. Display of the direct sequencing patterns revealed the existence of 136 heterogeneous loci among a total of 33 strains. The heterogeneous loci were detected only in the stem region designated helix 10. All of the substitutions conserved the relevant secondary structure. The 33 strains were divided into two groups: one group, including 22 strains, had less than two heterogeneous bases; the other group, including 11 strains, had five or more heterogeneous bases. The two groups were different in their combinations of heterogeneous bases. The former mainly contained transitional substitutions, and the latter was mainly composed of transversional substitutions, suggesting that at least two mechanisms, possibly misincorporation during DNA replication and horizontal gene transfer, cause rRNA heterogeneity.

Base Composition↗

Structure of the heterogeneous L-S junction region of human cytomegalovirus strain AD169 DNA.

The genome of human cytomegalovirus strain AD169 contains a region of heterogeneity located at the junction between the long (L) and short (S) components of the viral DNA. Twelve cloned L-S junction fragments were studied by using the restriction enzymes HaeII and XhoI. The region of heterogeneity was localized within a single HaeII restriction fragment. The enzyme XhoI was used to subdivide this region and revealed the presence of three types of heterogeneity within the junction fragments. Each of the cloned junction fragments contained one of the following fragments: 0.553, 0.95, or 1.35 kilobase pairs (referred to as class I heterogeneity). Class II heterogeneity was defined as the presence of tandem duplications of class I fragments. In addition, a variable number (0 to 5) of a 0.2-kbp fragment (class III heterogeneity) was observed. Mapping of these fragments with partial XhoI digestions revealed that the class I and class III heterogeneous fragments were adjacent. The DNA sequence of the smallest cloned L-S junction fragment was determined and analyzed. This junction fragment contained a single 0.553-kbp XhoI fragment and no copies of the 0.2-kbp fragment. The 0.553-kbp XhoI fragment was similar in structure to the a-sequences of herpes simplex virus types 1 and 2. In addition, a region of homology was found between the a sequences of herpes simplex virus types 1 and 2 and the 0.553-kbp XhoI fragment from the human cytomegalovirus junction.

Base Sequence↗

Heterogeneous splenic enhancement patterns on spiral CT images in children: minimizing misinterpretation.

PURPOSE: To (a) determine the appearances and timing of heterogeneous splenic enhancement at spiral computed tomography (CT) and (b) identify variables influencing heterogeneous splenic enhancement. MATERIALS AND METHODS: Sequential isolevel (24-mAs) CT images of the spleen obtained at 6-second intervals after initiation of contrast material injection in 112 children (mean age, 4.5 years) were reviewed. Heterogeneity characteristics assessed included type, onset, maximum, and resolution. Relationship to variables (injection rate, age, splenomegaly) was assessed with the Fisher exact test. RESULTS: Eighty-one of the 112 patients (72%) had transient heterogeneity: archiform (45 patients), diffuse (25 patients), and focal (11 patients). Mean times were as follows: initial visualization after onset of contrast material injection, 19.2 seconds; maximum heterogeneity, 27.3 seconds; and resolution, 47.4 seconds. Statistically significant relationships were seen between frequency of heterogeneity and injection rate (> or = 1 mL/sec, 82%; < 1 mL/sec, 50% [P = .001]), age (> 1 year, 76%; < or = 1 year, 46% [P = .04]), and splenomegaly (present, 20%; absent, 77% [P = .048]). CONCLUSION: Heterogeneous splenic contrast enhancement is common, has several patterns of appearance, and is predictably encountered during the 70 seconds after the initiation of contrast material injection. Injection rate, age, and presence of splenic disease influence the frequency with which these artifacts are encountered.

Artifacts↗

Relationship between structural and hemodynamic heterogeneity in microvascular networks.

The relationship between structural and hemodynamic heterogeneity of microvascular networks is examined by analyzing the effects of topological and geometric irregularities on network hemodynamics. Microscopic observations of a network in the rat mesentery provided data on length, diameter, and interconnection of all 913 segments. Two idealized network structures were derived from the observed network. In one, the topological structure was made symmetric; in another a further idealization was made by assigning equal lengths and diameters to all segments with topologically equivalent positions in the network. Blood flow through these three networks was simulated with a mathematical model based on experimental information on blood rheology. Overall network conductance and pressure distribution within the network were found to depend strongly on topological heterogeneity and less on geometric heterogeneity. In contrast, mean capillary hematocrit was sensitive to geometric heterogeneity but not to topological heterogeneity. Geometric and topological heterogeneity contributed equally to the dispersion of arteriovenous transit time. Hemodynamic characteristics of heterogeneous microvascular networks can only be adequately described if both topological and geometric variability in network structure are taken into account.

Animals↗

Modeling the effect of flow heterogeneity on coronary permeability-surface area.

In 11 anesthetized pigs, the left anterior descending coronary artery (LAD) was cannulated and pump perfused with blood before and during maximum adenosine vasodilation. For LAD plasma flows (F) ranging from 0.42 to 3.6 ml.min-1.g perfused tissue-1, we injected radiolabeled microspheres to measure heterogeneity and used the multiple indicator-dilution method to measure permeability-surface area product (PS) for EDTA. Heterogeneity of flow from the LAD was expressed as relative dispersion (RD) = standard deviation of flow/mean flow. Values of RD, corrected for tissue sample size using fractal theory, ranged from 13 to 87%, approaching 16-35% at high F. We developed a "variable-recruitment model" of regional heterogeneous capillary transport to correct PS for flow heterogeneity and capillary surface area recruitment. Values of PS ranged from 0.14 to 0.96 ml.min-1.g-1. Accounting for heterogeneity increased PS values by 0-18% compared with homogeneous values. Results revealed PS to be proportional to flow up to F = 1.5-2.1 ml.min-1.g-1 and then was constant at higher flows. The initial increase of PS with F may be due to capillary recruitment. When full recruitment is reached, PS becomes independent of F. We conclude that flow heterogeneity is significant but not readily predictable in the pig myocardium and that the use of microspheres to correct indicator-dilution data for flow heterogeneity improves the interpretation of multiple-tracer studies, particularly when tracers are used to study interventions that may alter flow distribution.

Anesthesia↗

Mechanical analysis of heterogenic inhibition between soleus muscle and the pretibial flexors in the cat.

1. The role of proprioceptive pathways linking the direct antagonists soleus (S) and tibialis anterior (TA) muscles in governing the mechanical properties of the ankle joint were studied in the decerebrate cat. Actions of these heterogenic pathways were compared with those between S and extensor digitorum longus (EDL), a muscle that also acts at the metatarsophalangeal joint. These neurally mediated interactions between S and either TA or EDL were studied by applying controlled length changes to the isolated tendons of pairs of these muscles and recording the resulting changes in force. The muscles were activated with the use of electrically evoked crossed-extension reflexes, flexion reflexes, and brain stem stimulation. 2. Heterogenic inhibition from TA or EDL onto S was well developed whether S was initially quiescent or activated by a crossed-extension reflex. The inhibition persisted for the duration of the stretch of TA or EDL. During a crossed-extension reflex, TA did not generate background force, but brief stretch reflexes could be obtained. During flexion reflexes, stretch reflexes in S were usually abolished, and heterogenic inhibition from S to TA was weak or absent. 3. The strength of the heterogenic inhibition onto S was dependent on the initial length and activation level of TA and EDL. Changes in flexor length or activation level per se did not alter the background force or strength of the stretch reflex in S. Even taking into account the variation of strength of inhibition with the initial state of the muscle of origin, the strength of the inhibition was stronger from TA to S than the other way around. 4. The contributions of heterogenic inhibition from TA and EDL to S were independent in the sense that these components summed linearly with each other and with the autogenic reflex in S. In addition, the magnitude of the inhibition from TA to S was proportional to the amplitude of stretch for low to intermediate levels of initial force in S. The inhibition appeared to affect the mechanical responses of S essentially as rapidly as the stretch reflex in this muscle. 5. The heterogenic inhibition from TA to S was reduced or abolished by intravenous injections of strychnine but unaffected by injections of picrotoxin or bicuculline. These results, together with the observation that the inhibition sums linearly with the stretch reflex, suggest that the mechanism of this heterogenic inhibition is glycinergic and postsynaptic and, therefore, may include Ia-disynaptic reciprocal inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗