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Growth of Enterobacter aerogenes in a chemostat with double nutrient limitations.

The behavior of Enterobacter aerogenes during growth in chemostats limited by single and double nutrient restrictions was examined. On the assumption that different essential nutrients act to limit growth in different ways, we selected pairs of nutrients likely to affect different aspects of metabolism. Results show that macromolecular cell composition can be controlled by using more than one nutrient restriction. The polysaccharide content of the cells is readily manipulated by the ratio of carbon to nitrogen in the inlet nutrients. Also, at low dilution rates, ratios of protein to ribonucleic acid are dependent on the ratio of phosphate to nitrogen in the input nutrients. An examination of both acetic acid and metabolite production (as measured by ultraviolet absorbance of culture filtrates) showed that accumulation of these products was dependent on both dilution rate and type of nutrient limitation(s). These results were examined in terms of the problems of translation of batch to continuous culture processes and the use of selected nutrient limitations to control noncellular product formation.

Ammonia

Change from homo- to heterolactic fermentation by Streptococcus lactis resulting from glucose limitation in anaerobic chemostat cultures.

Lactic streptococci, classically regarded as homolactic fermenters of glucose and lactose, became heterolactic when grown with limiting carbohydrate concentrations in a chemostat. At high dilution rates (D) with excess glucose present, about 95% of the fermented sugar was converted to l-lactate. However, as D was lowered and glucose became limiting, five of the six strains tested changed to a heterolactic fermentation such that at D = 0.1 h(-1) as little as 1% of the glucose was converted to l-lactate. The products formed after this phenotypic change in fermentation pattern were formate, acetate, and ethanol. The level of lactate dehydrogenase, which is dependent upon ketohexose diphosphate for activity, decreased as fermentation became heterolactic with Streptococcus lactis ML(3). Transfer of heterolactic cells from the chemostat to buffer containing glucose resulted in the nongrowing cells converting nearly 80% of the glucose to l-lactate, indicating that fine control of enzyme activity is an important factor in the fermentation change. These nongrowing cells metabolizing glucose had elevated (ca. twofold) intracellular fructose 1,6-diphosphate concentrations ([FDP](in)) compared with those in the glucose-limited heterolactic cells in the chemostat. [FDP](in) was monitored during the change in fermentation pattern observed in the chemostat when glucose became limiting. Cells converting 95 and 1% of the glucose to l-lactate contained 25 and 10 mM [FDP](in), respectively. It is suggested that factors involved in the change to heterolactic fermentation include both [FDP](in) and the level of lactate dehydrogenase.

Acetates

Response of Rhodopseudomonas capsulata to illumination and growth rate in a light-limited continuous culture.

Rhodopseudomonas capsulata was grown under anaerobic, photosynthetic conditions in a continuous culture device. Under light limitation, at a constant dilution rate, it was shown that cell composition, including photopigment (bacteriochlorophyll and carotenoids) and ribonucleic acid content, was not affected by incident light intensity; however, steady state culture density varied directly and linearly with light intensity. On the other hand, photopigment and ribonucleic acid levels were affected by growth rate regardless of light intensity. Additional experiments indicated a high apparent Ks for growth of R. capsulata with respect to light. These results were interpreted to mean that near the maximum growth rate (D = 0.45 h-1) some internal metabolic process became the limiting factor for growth, rather than the imposed energy limitation. A mathematical expression for the relation between steady-state culture density and dilution rate was derived and was found to adequately describe the data. A strong correlation was found between continuous cultures limited either by light or by a chemical energy source.

Bacteriochlorophylls

Radiorespirometry of Candida utilis in phased culture under nitrogen-, carbon-, and phosphorus-limited growth.

The release of 14CO2 from specifically labelled glucose ([G-1-14C],[G-2-14C],[G-3,4-14C], and [G-6-14C]) by phased cells of C. utilis was examined at intervals during 6-h cycles under conditions of N-,P-, and C-limited growth. On the basis that the release of 14CO2 from [G-1-C14] could serve as a measure of hexose monophosphate pathway (HMP) activity, of 14CO2 from [G-3,4-14C] as a measure of Embden-Meyerhof-Parnas (EMP) activity, and 14CO2 from [G-6-14C] as indicative of tricarboxylic acid (TCA) cycle activity, it was concluded that a relatively uniform operation of EMP occurred throughout the cycle in N-, P-, and C-limited cells, and of HMP and TCA in C-limited cells, but considerable variations took place in HMP and TCA cycle activities in N- and P-limited cells. The patterns of 14CO2 released from [G-2-14C] were more closely related to those observed from [G-1-14C] and [G-3,4-14C] than from [G-6-14C]. Changes in the rate of 14CO2 evolution during the cycle were sometimes abrupt and likely coincided with 'critical points' of metabolic activity in the cycle.

Candida

Wind speed limits to work under hot environments for clothed men.

Four heat-acclimated clothed young adult men exercised (treadmill) at metabolic rate of 191 W.m-2 (27% VO2 max), under five air temperatures (Ta) between 36 and 53 degrees C and three wind velocities (v), 1, 2, and 4 m.s-1, for 2 h. The 2nd h of each experiment involved progressive increases in the ambient vapor pressure (Pa) to force an upward inflection of the rectal temperature (Tre). The Tre point of inflection identified the critical Pa (Pcrit) for each Ta. The average mean skin temperature (Tsk = 36 degrees C for all Pcrit. Straight-line isotherms for Tsk = 36 degrees C, which agreed with the negative regressions of the Pcrit on Ta, represented the limits of exposure for Ta less than or equal to 44 degrees C. The slope characteristics of the isotherms corresponded with skin wettedness (w) of 0.94, 0.71, and 0.58, respectively, for v of 1, 2, and 4 m.s-1. For Ta greater than 44 degrees C the limit line corresponded with steeper negative regressions indicating a lower w than for Ta less than or equal to 44 degrees C. Despite the increase in the ambient evaporative capacity due to the higher v the limit lines describing exposure limits were not significantly different either at Ta less than or equal to 44 degrees C for v of 2 and 4 m.s-1 or at Ta greater than 44 degrees C for all three v.

Acclimatization

[Limiting behavior of a model of the impulse activity of a neuron for large frequency of input flow and small contributions of a single synapse (non-diffusion approximation)].

The limit behavior of probability models of neuron's firing, viz. models with exponential decay and constant threshold is considered. These models differ from each other by F(v), distribution of jumps of potential after arrival of input impulse. If average number of input impulses arriving during the decaying time of one impulse in very large and threshold depolarisation, measured by unit of average jump of potential, is large too, than limit density of interspike interval distribution does not depend on form of F(v); and depends on other neuron's parameters mean and variance of F(v). Moreover, the form of this density depends on only one parameter--normalised threshold. Under this condition interspike interval distribution for diffusion model converges to the same limit. Lapase transform for limit distribution is found and results of its numeric inverts are given.

Action Potentials

Influence of a between-run component of variation, choice of control limits, and shape of error distribution on the performance characteristics of rules for internal quality control.

A computer-stimulation study has been performed to determine how the performance characteristics of quality-control rules are affected by the presence of a between-run component of variation, the choice of control limits (calculated from within-run vs. total standard deviations), and the shape of the error distribution. When a between-run standard deviation (Sb) exists and control limits are calculated from the total standard deviation (St, which includes Sb as well as the within-run standard deviation, Sw), there is generally a loss in ability to detect analytical disturbances or errors. With control limits calculated from Sw, there is generally an increase in the level of false rejections. The presence of non-gaussian error distribution appears to have considerably less effect. It can be recommended that random error be controlled by use of a chi-square or range-control rule, with control limits calculated from Sw. Optimal control of systematic errors is difficult when Sb exists. An effort should be made to reduce Sb, and this will lead to increased ability to detect analytical errors. When Sb is tolerated or accepted as part of the baseline state of operation for the analytical method, then further increases in the number of control observations will be necessary to achieve a given probability for error detection.

Chemistry, Clinical

Prevalence and risk factors of red blood cell alloimmunization among sickle cell disease patients in resource-limited countries: A systematic review and meta-analysis.

BACKGROUND: Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by hemoglobin S production, in which homozygous individuals (HbSS) develop a broad range of acute and chronic complications. While disease-modifying and curative therapies are increasingly available in high-income settings, red blood cell (RBC) transfusion remains the mainstay of treatment in resource-limited countries and is associated with high rates of alloimmunization. This systematic review and meta-analysis aimed to estimate the prevalence of alloimmunization and identify associated risk factors among patients with SCD living in resource-limited settings. METHODS: Africa Journals Online (AJOL), Embase, PubMed, Scopus, and Web of Science were searched for original studies published from inception to December 15, 2025. Only studies conducted in low- and lower-middle-income countries (LMICs) were included. Eligible studies evaluated the prevalence of alloimmunization in patients with SCD receiving RBC transfusions. A random-effects meta-analysis of proportions was performed to pool quantitative data, while qualitative findings were systematically summarized in tabular form. Statistical heterogeneity was assessed using the I² statistic and further explored using Baujat plots, leave-one-out analyses, and meta-regression. RESULTS: Our analysis included 27 studies conducted in Africa (n = 23) and Asia (n = 4), predominantly from lower-middle-income countries (n = 19) and mainly employing a cross-sectional design (n = 20), comprising 3128 previously transfused patients with SCD. The pooled prevalence of RBC alloimmunization was 8.76% (95% CI: 6.71-11.37%; I² = 75%). Higher alloimmunization rates were observed in West and North Africa, particularly in Côte d'Ivoire, Egypt, and Nigeria, whereas lower rates were reported in Asia and East Africa. The most frequently identified antibodies belonged to the Rh blood group system (n = 153), followed by the Kell system (n = 65). CONCLUSION: In resource-limited settings, RBC alloimmunization is a frequent and clinically significant complication in patients with SCD, contributing to increased morbidity and potential mortality. Targeted and economically viable antigen matching may reduce alloimmunization rates and improve transfusion safety in LMICs.

Humans

A scalable HPC framework for bioinformatics in resource-limited settings: design principles, implementation, and sustainability from the UVRI experience.

MOTIVATION: Building and sustaining High-Performance Computing (HPC) infrastructure for bioinformatics research in resource-limited settings presents significant technical, financial and operational challenges. Institutions in low-and middle-income regions often face constraints such as limited technical expertise, unstable infrastructure and restricted funding which can hinder the deployment of large-scale computational platforms necessary for modern genomics and bioinformatics analyses. RESULTS: We present a scalable and modular HPC framework developed at the Uganda Virus Research Institute (UVRI) to support large-scale genomics and other omics data analyses in resource-limited settings. The framework integrates open-source HPC management tools, infrastructure automation, and reproducible configuration management to enable reliable deployment and maintenance. Optimized storage and networking configurations combined with a phased capacity-building strategy support high-throughput genomic workflows while strengthening local technical expertise. From our implementation experience, we derive ten practical design and operational rules that provide a transferable methodology for establishing and sustaining in-house HPC infrastructure. These rules emphasize strategic investment in human capacity, structured planning, leveraging collaborations, adoption of open-source technologies and service management practices to improve operational resilience and long-term sustainability. AVAILABILITY: The design principles, automation strategies and implementation guidelines described in this work are applicable to institutions seeking to establish sustainable HPC resources for bioinformatics research in resource-constrained environments.

Computational Biology

Light cells within the limiting membrane of rat seminiferous tubules.

Light-staining cells, distinct from myoid cells, were identified in electron micrographs of the limiting membrane of rat seminiferous tubules. While these cells were also found free in the interstitial space, they were observed mostly in the myoid cell layer of the limiting membrane but were never seen within the seminiferous epithelium itself. The light cells were characterized by a pale-stained cytoplasm containing a spheroidal Golgi apparatus next to a polymorphous often kidney-shaped nucleus, a few cisternae of rough endoplasmic reticulum and some granules of various types including a multivesicular bodies. In hematoxylin-stained whole mounts of dissected tubules, these light cells were readily identified under the light microscope by nuclear morphology and light-staining juxtanuclear Golgi apparatus. The incidence of these cells, per unit surface area of tubular wall, was calculated, taking into consideration the stages of the cylce of the seminiferous epithelium with which they were associated. Distributed along the entire length of seminiferous tubules, their number varied significantly during the cycle. Low numbers were found in stages II-IV and XIII of the cycle while high numbers were found in stages IX to XII and XIV-I of the cycle. These observations indicate that the seminiferous epithelium may exert an influence on the population of light cells present in the tubular limiting membrane.

Animals

Elastic tissue in the limiting membrane of the human seminiferous tubule.

The structure and distribution of elastic tissue were studied in the limiting membrane of the seminiferous tubule from normal human testis. The elastic and elastic-related fibers (oxytalan and elaunin) were recognized by their tinctorial and ultrastructural characteristics. The connective structures of the limiting membrane, including the fibrotubules and the amorphous material of the elastic system, were studied after tannic acid-glutaraldehyde fixation. Fibrotubules (oxytalan fibers) were observed in almost all intercellular spaces of the limiting membrane, closely related to the contractile cells; the elaunin fibers (patches of amorphous material surrounded by bundles of fibrotubules) were evident in the outermost layers. The function of this system of elastic tissue and myoid cells is discussed, considering the permeability membrane and the role of the myoid cells in the elastogenesis and contractility of the seminiferous tubule.

Elastic Tissue

Testing with puromycin and amino acyl tRNAs that limit the rate of peptide chain extension.

With puromycin one can recognize when the synthesis of a given protein is dependent on amino acyl tRNA that is present in rate limiting amount. We demonstrate this use of puromycin by its interaction with another inhibitor, L-o-methylthreonine. L-o-methylthreonine lowers the Ile-tRNA concentration in the cell, thereby inhibiting synthesis of proteins containing isoleucine. In certain rabbits, the alpha hemoglobin chain has three isoleucyl residues and the beta chain none. L-o-methylthreonine thus inhibits alpha globin synthesis in intact reticulocytes from these rabbits. When puromycin and L-o-methylthreonine are used together, the two inhibitors synergize in inhibiting alpha globin synthesis. Hence, puromycin is a more effective inhibitor when the Ile-tRNA concentration is lowered. Cycloheximide and sodium fluoride have different modes of action from puromycin. Neither synergizes with L-o-methylthreonine; instead, the interaction is less than additive. We have found that beta chain synthesis in rabbit reticulocytes is more sensitive than alpha to inhibition by puromycin. This difference could reflect either differences in amino acid sequence or tRNA dependent limitations of beta chain elongation. The switch from fetal to adult hemoglobin in humans does not involve changes in limiting amino acyl tRNA because, for cord blood from infants of different developmental ages, the puromycin sensitivity of incorporation into gamma and beta chains remains constant.

Animals

Biomass yields of Chlorella from iron (Yx/Fe) in iron-limited batch cultures.

The maximum biomass in iron-limited photosynthetic batch cultures of chlorella increased as the logarithm of the iron concentration. The growth yield from iron (UxFe) showed a marked inverse relation to the specific growth rate. The maximum biomass yield, g dry biomass/g iron consumed, was 7.5 X 10(3) with specific growth rate 0.108h-1; the minimum was 0.79 X 10(3) with specific growth rate 0.145 h-1. The maximum specific growth rate in the exponential phase of Fe limited cultures varied as the initial Fe concentration. Fe-limited growth made the cells adhere to a glass surface.

Chlorella

Treatment of narcissistic problems in time-limited psychotherapy.

Time-limited psychotherapy is being used with an expanding variety of emotional disorders, often as the treatment of choice. Clinical experience indicates that this form of treatment can produce major and enduring improvements. Persons suffering from major narcissistic problems generally are assumed to be impervious to time-limited treatments. However, long-term treatment is becoming less feasible because of financial considerations. Time-limited psychotherapy can provide circumscribed symptomatic relief by fostering increased use of defensive intellectualization and related ego-coping skills. Transference interpretations directed toward connecting maladaptive behavior patterns outside of therapy to past childhood relationship patterns proved most effective.

Defense Mechanisms

Limitations of the computer in electrocardiographic interpretation.

Use of the computer for electrocardiographic interpretation has steadily increased over the past decade. Although acceptance by a majority of physicians has been slower than originally anticipated, it now appears assured. Nevertheless, the approach has limitations. These are primarily a result of the lack of objectivity in clinical electrocardiographic criteria for both measurement and diagnosis. The limitations are best judged by reviewing experience with a variety of programs. Currently this still involves abstracting from the reports of developers. Although not all developers have analyzed every portion of their programs, in general the data from one program apply to others; that is, all are with minor exceptions at the same "state of the art." Awareness of the limits of computer performance allows a physician to use the computer properly in his current electrocardiographic practice.

Arrhythmias, Cardiac

Kinetic factors limiting the synthesis of ATP by chromatophores exposed to short flash excitation.

ATP synthesis was measured after chromatophores from Rhodopseudomonas capsulata had been subjected to illumination by single turnover flashes fired at variable frequencies. Three processes were examined, which under different conditions can limit the net yield of ATP. (1) A process with an apparent relaxation time of 10-20 ms. This reaction probably limits the rate of ATP synthesis in continuous illumination. It has similar time dependence to the stimulation of the carotenoid shift decay by ADP after a single flash. (2) An active state of the ATPase only persists when the chromatophores are excited more often than once in 10 s. This state decays with similar kinetics to the entire carotenoid shift decay. Full activation is achieved after two flashes. (1) and (2) are not significantly affected by concentrations of antimycin A sufficient to block electron flow through the cytochrome b/c2 oxidoreductase and abolish phase III in the generation of the carotenoid shift. (3) In the presence of antimycin A, after the third, fourth and subsequent flashes ATP synthesis is limited by the quantity of reducing equivalents transported through the reaction centre rather than by the level of the electrochemical proton gradient.

Adenosine Triphosphate

Diffusion-limited ion flow through pores.

If the permeability of an ion channel is high, the overall transport becomes ultimately limited by the rate with which ions from the aqueous phase arrive at the mouth of the channel. In this study a theoretical treatment of diffusion-limited ion transport through pores is given which takes both concentration and electric potential gradients into account as driving forces for the flow of ions. The current-voltage characteristic of a diffusion-limited channel is found to be strongly saturating. Addition of an impermeable elesults from a reduction in the electric field strength near the mouth of the channel. At low voltages the permeability P of the pore is obtaines as 1/P =(1/Pi)+(1/P'c)+(1/P''c) where Pi is the intrinsic permeability and P'c, P''c are the left-hand and right-hand convergence permeabilities, respectivelyl which are proportional to the aqueous diffusion coefficient of the permeable ion and to the effective capture radius of the pore.

Biological Transport

Rate-limiting factors for lymphocyte protein synthesis. Ribosome commitment and the capacity of lymphocyte cell-free systems to translate exogenous mRNAs.

The properties of the protein synthesising systems of different lymphocyte preparations have been compared with those of non-lymphoid tissues. Polysome profiles from rat thymocytes, sheep mesenteric lymphocytes, rat liver and mouse ascites tumours showed that the commitment of ribosomes to protein synthesis in lymphocytes was relatively low. Initiation factor activities, assessed on the abilities of post-mitochondrial fractions to support exogenous mRNA translation, were limited or undetectable in lymphoid tissues. While the thymocyte system translated globin mRNA, the response was enhanced by ascites extracts rich in initiation factors. The mesenteric lymphocyte system responded only marginally to globin mRNA and poly(U) but the responses were not enhanced by ascites extracts. The activity of isolated mesenteric ribosomes was comparable with ribosomes from other tissues, indicating that extraribosomal factors were responsible for the poor overall activity of the mesenteric system. Finally, the effects of cycloheximide on the recruitment of polysomes in lymphocytes indicated that the commitment of ribosomes to protein synthesis might be restricted by both limited mRNA availability and limited capacity for initiation of mRNA translation.

Animals