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Results for “Process optimization”

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PubMed1985

Solubilization and reconstitution of rat liver mitochondrial carnitine acylcarnitine translocase.

Carnitine acylcarnitine translocase has been solubilized from inverted inner membrane vesicles of rat liver mitochondria with octyl glucoside and reconstituted into asolectin liposomes. For both processes, optimization of the detergent to phospholipid ratio was found crucial for obtaining reconstitutively active liposomes. Reassembly of the solubilized carrier into asolectin liposomes was achieved either by the octyl glucoside dilution method or by Extracti-Gel D column chromatography. The reconstituted system catalyzed exchange diffusion of carnitine, exhibited the expected inhibitor and temperature sensitivity, and discriminated between stereoisomers of octanoylcarnitine. The activity of unidirectional import of carnitine was low compared to exchange diffusion. It showed high-temperature sensitivity and a loss of activity on prolonged sonication that was regained by an appropriate freeze-thaw step subsequently.

Animals↗

PubMed1991

A novel method for optimum biopsy specimen preservation for histochemical and immunohistochemical analysis.

A novel method has been developed for optimally processing biopsy specimens combining freeze-substitution with low-temperature plastic embedding. Immunohistochemistry and conventional histochemical stains were all readily performed on tissue displaying high-quality morphologic preservation. Labile antigens, especially lymphoid cell surface antigens, were well preserved. This new method avoids the need for tissue fixation and combines the superior morphologic preservation of fixed embedded tissue with the reactivity of cryostat sections. This method ensures that diagnostic information from even the smallest biopsy specimen is maximized because a wide range of phenotypic markers can be applied and evaluated in relation to high-quality morphologic preservation of tissue. Biopsy specimens are stored at room temperature without loss of tissue-specific characteristics during storage.

Acetone↗

PubMed1989

TEFOOL/2: a program for theoretical drug design on microcomputers.

TEFOOL/2, a program written in BASIC, is presented in this paper. The purpose of TEFOOL/2 is to provide people interested in drug design with an easy-to-handle program where some of the most important techniques in QSAR are included. The program permits the selection of the training series, performs regression calculations and searches for optimum substituents. The latter is achieved by using either a Hansch's strategy or geometrical procedures. The program is interactive and can be implemented on an IBM-PC or compatible microcomputer. Although TEFOOL/2 has been developed for its application in drug design studies, its great flexibility makes it suitable for application to any experimental design or optimization process.

Algorithms↗

PubMed2025

Unicorn: enhancing single-cell Hi-C data with blind super-resolution for 3D genome structure reconstruction.

MOTIVATION: Single-cell Hi-C (scHi-C) data provide critical insights into chromatin interactions at individual cell levels, uncovering unique genomic 3D structures. However, scHi-C datasets are characterized by sparsity and noise, complicating efforts to accurately reconstruct high-resolution chromosomal structures. In this study, we present ScUnicorn, a novel blind super-resolution framework for scHi-C data enhancement. ScUnicorn uses an iterative degradation kernel optimization process, unlike traditional super-resolution approaches, which rely on downsampling, predefined degradation ratios, or constant assumptions about the input data to reconstruct high-resolution interaction matrices. Hence, our approach more reliably preserves critical biological patterns and minimizes noise. Additionally, we propose 3DUnicorn, a maximum likelihood algorithm that leverages the enhanced scHi-C data to infer precise 3D chromosomal structures. RESULTS: Our evaluation demonstrates that ScUnicorn achieves superior performance over the state-of-the-art methods in terms of Peak Signal-to-Noise Ratio, Structural Similarity Index Measure, and GenomeDisco scores. Moreover, 3DUnicorn's reconstructed structures align closely with experimental 3D-FISH data, underscoring its biological relevance. Together, ScUnicorn and 3DUnicorn provide a robust framework for advancing genomic research by enhancing scHi-C data fidelity and enabling accurate 3D genome structure reconstruction. AVAILABILITY AND IMPLEMENTATION: Unicorn implementation is publicly accessible at https://github.com/OluwadareLab/Unicorn.

Single-Cell Analysis↗

PubMed1989

Biochemical engineering challenges of purifying useful proteins.

Some of the biochemical engineering issues that arise when the purification of proteins is scaled up are examined. The first question addressed is the quantity of various proteins likely to be required. Consideration is given to the order in which isolation procedures may be applied and to the selective removal on a large scale of non-proteinaceous materials. Some general problems such as the effect of mechanical forces on proteins and their complexes and aggregates are examined, together with ways of enhancing the properties of these aggregates and the methods of recovering them. The manner in which on-line process optimization can be achieved during pilot plant trials is discussed and the paper concludes with a summary of new scientific developments to which the biochemical engineer will need to respond.

Biotechnology↗

PubMed1989

Paraplegic standing controlled by functional neuromuscular stimulation: Part II--Computer simulation studies.

We simulated two types of body motion. First, the body position is assumed to be initially perturbed from the upright position, and all muscles are assumed inactive at the initial position. The control law developed in the preceding paper drives the body segments to the standing position. Arm movements are then applied to the body to investigate how performance is affected by an external disturbance. Simulated body motion indicated that the current output-feedback control law functions well. The body can recover upright posture from a highly flexed position, and the controller can then maintain the body near the vertical during arm movements. The simulation results showed three consistent activation patterns based on energy minimization: 1) no antagonistic muscle pairs are coactivated, 2) strong muscles are recruited before weak ones, and 3) fast muscles are recruited before slow ones. The reason for the second and third observations is that energy liberation rate depends heavily on the relative amount of muscle activation. Since the current control law requires muscles to generate specific joint torques at a prescribed time, strong muscles do not have to be activated as much as weak ones, and recruiting a fast muscle at low activation level consumes less energy than recruiting a slow one at high activation level. Although the output-feedback control law functions well according to our simulation results, the static optimization process would, in practice, take too much computational time to make it practical. Based on the consistent activation patterns found in our simulations, we therefore developed a simpler (suboptimal) activation-distribution scheme that takes much less time and still gives nearly identical performance.

Biomechanical Phenomena↗

PubMed1986

Monoclonal antibody labeling of mononuclear cell surface antigens in formaldehyde-fixed paraffin-embedded cutaneous tissue.

The influence of the sequential stages of conventional formaldehyde fixation and paraffin embedding of cutaneous tissue on monoclonal antibody labeling of cell surface antigens is described. The effects of variation in fixation time, dehydration, clearing, wax embedding, and enzyme treatment of cutaneous sections were examined. By curtailing fixation time, using cold ethanol dehydration, and limited cold clearing with xylene, immunoreactivity of several important monoclonal antibodies was retained. Wax embedding could be achieved at 58 degrees C for 1 h or by using low-melting-point wax at 42 degrees C for 3 h. Thus was derived an optimal processing procedure which afforded good tissue morphology and allowed reliable reproducible labeling by monoclonal antibodies to cell surface antigens.

Antibodies, Monoclonal↗

PubMed1990

Membrane and cytosolic interleukin-1 alpha and beta in normal human epidermal cells: variability of epitope exposure in immunohistochemistry.

Previous studies have shown that interleukin-1 (IL-1) is present in normal human epidermis. However, with immunohistochemical techniques, epidermal IL-1 immunoreactivity has been found in only a limited number of epidermal cells. In the present study, we show that both IL-1 alpha and beta immunoreactivities can be detected in all epidermal cell layers, provided optimal processing of tissue samples is used. The use of isolated epidermal cells showed that keratinocytes at various stages of maturation display both membrane-associated and cytosolic IL-1 alpha and beta immunoreactivities. After protease treatment of tissue sections, the IL-1 beta immunoreactivity of the granular cell layer was enhanced by some antibodies used, whereas in the other cell layers it was clearly lower. We a) suggest a different cellular localization, processing, and/or binding to subcellular structures of IL-1 during the differentiation process of human keratinocytes and b) outline the technical difficulties in any immunohistologic approach to IL-1 status in diseased skin.

Cell Membrane↗

PubMed1990

A new force-field program for the calculation of glycopeptides and its application to a heptacosapeptide-decasaccharide of immunoglobulin G1. Importance of 1-6-glycosidic linkages in carbohydrate.peptide interactions.

Energetically favored conformations of glycopeptide 1 were calculated using the newly developed force-field program, GEGOP (geometry of glycopeptides). The three-dimensional structure of glycopeptide 1, which is part of the Fc fragment of IgG1, has been calculated. 1 contains 27 amino acid residues from Pro291 to Lys317 and a biantennary decasaccharide N-linked to Asn297. The conformations of the peptide and the carbohydrate parts are shown to be mutually dependent. Single glycosyl residues of 1 exhibit interaction energies of up to -31.8 kJ/mol with the peptide portion. Generally, only a few of the glycosyl residues of the oligosaccharide moiety express significant interaction energies with the peptide part. No easy prediction is possible of glycosyl residues which exhibit favorable interaction energies. However, in all of the calculated structures, the glycosyl residues of the 1-6-linked branches show strong attractive forces for the peptide part. 1-6-glycosidically linked branches can adopt a larger number of conformations than other linkages due to their high flexibility which allows more favorable interactions with proteins. We developed the GEGOP program in order to be able to study the preferred conformations of large glycopeptides. The program is based on the GESA (geometry of saccharides) program and utilizes the HSEA (hard sphere exo anomeric) force field for the carbohydrate part and the ECEPP/2 (empirical conformation energy program for peptides) force field [Némethy, G., Pottle, M. S. & Scheraga, H. A. (1983) J. Phys. Chem. 87, 1883-1887] for the peptide part. The GEGOP program allows the simultaneous relaxation of all rotational degrees of freedom of these glycoconjugates during the energy optimization process. Thus, mutual interactions between glycosyl and amino acid residues can be studied in detail.

Carbohydrate Conformation↗

PubMed1985

Lateral-position-based models of interaural discrimination.

This letter investigates the hypothesis that lateral position is the only cue available for interaural discrimination experiments using 500-Hz stimuli. The discussion of this hypothesis is in the context of comparisons of the experimental data to predictions of the "position-variable" model of binaural interaction. The model predicts the mean and variance of the subjective lateral position of stimuli used in the discrimination experiments, assuming that discrimination performance is based on optimal processing of this subjective position. To the extent that the laterality predictions of the model are accurate, data that are inconsistent with its predictions would also be problematical for any model based on the subjective laterality of a single binaural image. The predictions (at least qualitatively) describe much of the observed experimental data, including a number of results that have not been addressed by any previous theory. Nevertheless, the observed performance is significantly better than the corresponding predictions for three types of experiments in which the utility of the position cue has been eliminated by experimental design. We believe that our results indicate that changes in lateral position are the primary cue in most interaural discrimination experiments, but that secondary attributes of the perceptual images can be useful when performance based on position alone would be poor.

Auditory Perception↗

PubMed1986

Isolation of Listeria monocytogenes from raw milk.

During a recent outbreak of listeriosis, we examined 121 raw milk samples and 14 milk socks (filters). Listeria monocytogenes was recovered from 15 (12%) of 121 milk specimens and 2 (14%) of 14 milk socks. The optimal processing method consisted of cold enriching diluted milk for 1 month with culture to selective broth, followed by plating.

Agar↗

PubMed1979

Statistical principle and methodology in the NISAN system.

The NISAN system is a new interactive statistical analysis program package constructed by an organization of Japanese statisticans. The package is widely available for both statistical situations, confirmatory analysis and exploratory analysis, and is planned to obtain statistical wisdom and to choose optimal process of statistical analysis for senior statisticians.

Computers↗

PubMedDate not supplied

Phenotypic traits and regulatory role of RNA folding in molecular selection.

We concentrate on instances in which the phenotypic expression of information encoded in an RNA primary sequence might be revealed by the folding of the RNA itself. We have discovered that this situation finds concrete realization in the design of RNA molecules capable of maximizing the rate of autocatalytic synthesis when incubated with viral Q beta-replicase. This requires that we introduce the notion of phenotypic traits at the molecular level. Thus, the problem of finding RNA sequences whose phenotype favorably influences propagation amounts go finding RNA sequences which fold so as to optimize enzymatic performance and are in addition endowed with the proper recognition sites. The proof that these two problems are indeed equivalent has two steps: First we predict the metastable folded structures formed as a template RNA chain grows by sequential incorporation of nucleotides. The transient folded states appear to be involved in the regulation of the enzyme activity and they occur in a manner which is "oblivious" of thermodynamic time scales. Secondly, we compute the time-dependent activation energy for relaxation of each intermediate structure. This is done to establish constraints necessary for optimization of the regulatory role of RNA folding. The search for prospective template sequences is subject to such constraints. Our results aim at elucidating an optimization process realized by molecular selection in de novo (template-free) RNA synthesis by Q beta-replicase. We argue that the phenotype which mediates selection is given by metastable folding which emerges together with the printing of the genotype, that is, within the time span of a replication turnover.

Algorithms↗

PubMed2026

Induced pluripotent stem cell reprogramming: methodological evolution and challenges in clinical translation.

Cell reprogramming can transform somatic cells into induced pluripotent stem cells providing a platform for patient-specific disease modeling, drug screening and regenerative medicine research. Since the advent of OKSM-mediated reprogramming, the system of technical approaches has evolved continuously - from integrated viral vectors to non-integrated episomal systems and, more recently, chemical reprogramming and CRISPR approaches. The simultaneous advances in single-cell multi-omics, biomaterials engineering, and artificial intelligence have further refined the controllability and precision of the reprogramming process. Despite these innovations, problems persist that hinder clinical translation: incomplete epigenetic resetting, ongoing clonal heterogeneity, genomic instability in long-term culture, and the lack of standardized Good Manufacturing Practice protocols for large-scale manufacturing. This review summarizes the trajectory of iPSC reprogramming technologies, with special emphasis on the translational applicability of each modality. We evaluated viral and nonviral delivery systems, chemical reprogramming, strategies that aid gene editing, and emerging engineering platforms, including microfluidics, smart biomaterials, and artificial-intelligence-driven process optimization. We further identify the core "translational triltrilas", namely, the inherent tradeoffs between security, homogeneity, and scalability, and propose a comprehensive strategy to overcome these bottlenecks. By linking basic mechanistic understandings with industrial and regulatory considerations, this review aims to provide a route for transitioning iPSC technology from a laboratory tool to a clinically viable manufacturing platform.

clinical translation↗

PubMed2025

Marine endophytes: biosynthetic engines for novel bioactive metabolites.

Marine endophytes are prolific sources of structurally diverse secondary metabolites with significant pharmaceutical potential, including anticancer, antimicrobial, and antioxidant agents. However, their commercial utilization is hindered by genomic instability in axenic cultures and inconsistent metabolite yields. While current studies focus on symbiotic interactions and compound discover, critical gaps persist in harnessing their biosynthetic capabilities. This review synthesizes knowledge on marine fungal metabolites and proposes a paradigm shift toward resource-driven research. It addresses strain improvement limitations and suggests strategies like mutagenesis, protoplast fusion, and metabolic engineering to bolster production stability and efficiency. The paper also discusses biological process optimization, including fermentation tuning, inducer and precursor addition, and adsorbent use, to enhance natural product synthesis. By identifying these research gaps and proposing a strategic roadmap, the review advances the stable and scalable production of bioactive metabolites, unlocking the commercial and therapeutic potential of marine endophytic fungi.

bioactive metabolites↗

PubMed1979

Patients who amplify bodily sensations.

Patients troubled by symptoms, regardless of the degree of demonstrable disease, are subject to fources that cause them to amplify, focus upon, and worry about these bodily perceptions. These forces are psychological, sociocultural, or part of the medical care process. Optimal management of the symptomatic and somatizing patient thus entails obtaining psychological information about emotional precipitants, relevant childhood experiences, psychiatric disorders, and the personal meaning of the symptom; searching for the somatizing personality themes of masochism and guilt, hostility, and dependence; understanding the patient's goals in obtaining medical care, such as information and explanation, psychological counseling, or social and administrative intervention; and assessing situational stress, secondary gain, and ethnic and cultural forces that foster the amplification of physical symptoms.

Anxiety↗

PubMed1992

Strategies for automated sequencing of human mitochondrial DNA directly from PCR products.

A rapid, robust and sensitive method has been developed for the amplification and direct sequencing of human mitochondrial DNA. A 403-bp hypervariable segment was amplified by two successive rounds of nested PCR. This was then sequenced by the dideoxy chain termination method using dye-labeled universal sequencing primers in conjunction with an automated DNA sequencer. This paper describes the assessment of four different strategies for this amplification and sequencing process. Optimal results were obtained by immobilizing the biotinylated PCR product on Dynabeads followed by solid-phase sequencing with Sequenase. Degraded samples and those containing trace amounts of DNA such as extracts from hair shafts can be analyzed by this method.

Automation↗

PubMed1990

Suspension culture of mammalian cells.

Mammalian cell suspension culture systems are being used increasingly in the biotechnology industry. This is due to their many advantages including simplicity and homogeneity of culture. Suspension systems are very adaptable (e.g., for microcarrier, microencapsulation, or other methods of culture). Their engineering is thoroughly understood and standardized at large scale, and automation and cleaning procedures are well established. Suspension systems offer the possibility of quick implementation of production protocols due to their ability to be scaled easily once the basic culture parameters are understood. The only main disadvantage of the suspension culture systems to date is their inapplicability for the production of human vaccines from either primary cell lines or from normal human diploid cell lines (Hayflick et al., 1987 and references therein). One of the great advantages of suspension culture is the opportunity it provides to study interactions of metabolic and production phenomena in chemostat or turbidostat steady-state systems. Furthermore, in suspension culture systems from which cell number and cell mass measurements are easy to obtain, rigorous and quantitative estimations of the effects of growth conditions or perturbations of metabolic homeostasis can be made. Such studies can speed up the development of optimal processes. With our increasing understanding of factors influencing expression in mammalian cells (Cohen and Levinson, 1988; Santoro et al., 1988) and the direct application of new methods in suspension culture (Rhodes and Birch, 1988), its usefulness and importance is likely to increase in the future. In this chapter, we have described some of the potential uses of the various suspension culture systems and have covered most of the established technology and literature. Due to the rapid developments and needs in the biotechnology industry and the versatility of suspension culture systems, it is probable that many more variations on this theme will evolve in the near future at both the pilot and production scales.

Animals↗