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PubMed1999

The archaeal molecular chaperone machine: peculiarities and paradoxes.

A major finding within the field of archaea and molecular chaperones has been the demonstration that, while some species have the stress (heat-shock) gene hsp70(dnaK), others do not. This gene encodes Hsp70(DnaK), an essential molecular chaperone in bacteria and eukaryotes. Due to the physiological importance and the high degree of conservation of this protein, its absence in archaeal organisms has raised intriguing questions pertaining to the evolution of the chaperone machine as a whole and that of its components in particular, namely, Hsp70(DnaK), Hsp40(DnaJ), and GrpE. Another archaeal paradox is that the proteins coded by these genes are very similar to bacterial homologs, as if the genes had been received via lateral transfer from bacteria, whereas the upstream flanking regions have no bacterial markers, but instead have typical archaeal promoters, which are like those of eukaryotes. Furthermore, the chaperonin system in all archaea studied to the present, including those that possess a bacterial-like chaperone machine, is similar to that of the eukaryotic-cell cytosol. Thus, two chaperoning systems that are designed to interact with a compatible partner, e.g., the bacterial chaperone machine physiologically interacts with the bacterial but not with the eucaryal chaperonins, coexist in archaeal cells in spite of their apparent functional incompatibility. It is difficult to understand how these hybrid characteristics of the archaeal chaperoning system became established and work, if one bears in mind the classical ideas learned from studying bacteria and eukaryotes. No doubt, archaea are intriguing organisms that offer an opportunity to find novel molecules and mechanisms that will, most likely, enhance our understanding of the stress response and the protein folding and refolding processes in the three phylogenetic domains.

Archaea↗

PubMed2001

[Study on anodic oxidation and hydrothermal treatment of titanium implants with thin hydroxyapatite layers: an implantational test in rabbits].

OBJECTIVE: To learn bone response to commercially pure titanium implants with anodic oxidation followed by hydrothermal treatment in vivo. METHODS: Tweleve rabbits were averagely divided into three groups. And 36 implants (9 polished, 9 roughened by grit-blasting, 9 treated with anodic oxidation followed by heat treatment and 9 treated with anodic oxidation followed by hydrothermal treatment) were randomly implanted into femur bones of each group rabbits. Implants were harvested at 4 W, 8 W and 16 W respectively. Slice about 30 microns thick were ground with a grinding machine and stained with 1% toluidine blue. The bone-implant interface was observed with light microscopy and scanning electron microscopy. Implant surface element contents were also detected with EDAX. RESULTS: Woven bone rapidly transferred to lamellae bone at 8 weeks for anodic oxidized implants followed by hydrothermal treatment, which appeared little woven bone and no hydroxyapatite debris between the interfacial zone at 16 weeks. In addition, Ca and P contents increased much more for hydrothermal treated implants after implantation compared with polished implants. CONCLUSIONS: Anodic oxidation followed with hydrothermal treatment of a titanium fixture could speed up woven bone transferring the lamellae bone at early time of implantation, which meant thin HA layers could accelerate bone healing at the implanted site and might shorten healing time. This superiority need more research in the future.

Animals↗

PubMed2026

Nanocarrier-Based Gene Delivery Systems: Mechanisms, Clinical Translation, and Future Perspectives.

Gene therapy holds revolutionary potential for managing genetic disorders, cancers and infectious illnesses. However, one of the biggest challenges is delivering DNA or RNA into targeted cells and in the safe and effective way. In this review, nano carrier-based approaches for gene delivery are critically examined, focusing on both viral and non-viral systems. The advancement of CRISPR-Cas genome editing, machine learning-assisted nanocarrier optimization, and biologically inspired delivery systems is being quickly pushed forward in this area. In this review, a comparative analysis of gene delivery systems is being provided, and the key challenges to clinical translation are being pointed out. In addition, expert opinions on future research directions are being offered, with a heavy focus on the development of multifunctional, precisely targeted, and easily scalable delivery systems that can be integrated with next-generation therapeutic technologies.

Humans↗

PubMedDate not supplied

Technology-based vs. traditional instruction. A comparison of two methods for teaching the skill of performing a 12-lead ECG.

The purpose of this study was to compare the effectiveness of an interactive, multimedia CD-ROM with traditional methods of teaching the skill of performing a 12-lead ECG. A randomized pre/posttest experimental design was used. Seventy-seven baccalaureate nursing students in a required, senior-level critical-care course at a large midwestern university were recruited for the study. Two teaching methods were compared. The traditional method included a self-study module, a brief lecture and demonstration by an instructor, and hands-on experience using a plastic manikin and a real 12-lead ECG machine in the learning laboratory. The second method covered the same content using an interactive, multimedia CD-ROM embedded with virtual reality and supplemented with a self-study module. There were no significant (p < .05) baseline differences in pretest scores between the two groups and no significant differences by group in cognitive gains, student satisfaction with their learning method, or perception of self-efficacy in performing the skill. Overall results indicated that both groups were satisfied with their instructional method and were similar in their ability to demonstrate the skill correctly on a live, simulated patient. This evaluation study is a beginning step to assess new and potentially more cost-effective teaching methods and their effects on student learning outcomes and behaviors, including the transfer of skill acquisition via a computer simulation to a real patient.

Adult↗

PubMed2000

Nickel containing CO dehydrogenases and hydrogenases.

The two redox catalysts described here can generate very low potential electrons in one direction and perform chemically difficult reductions in the other. The chemical transformations occur at unusual metal clusters. Spectroscopic, crystallographic, and kinetic analyses are converging on answers to how the metals in these clusters are arranged and how they are involved in the chemical and redox steps. The first structure of CO dehydrogenase, which will appear in the next year, will help define a firm chemical basis for future mechanistic studies. In the immediate future, we hope to learn whether the hydride intermediate in hydrogenase or the carbonyl intermediate in CO dehydrogenase bind to the Ni or Fe subsites in these heterometallic clusters. Or perhaps could they be bridged to two metals? Inter- and intramolecular wires have been proposed that connect the catalytic redox machine to proximal redox centers leading eventually to the ultimate redox partners. Elucidating the pathways of electron flow is a priority for the future. There is evidence for molecular channels delivering substrates to the active sites of these enzymes. In the next few years, these channels will be better defined. The products of CO2 and proton reduction are passed to the active sites of other enzymes and, in the case of H2, even passed from one organism to another. In the future, the mechanism of gas transfer will be uncovered. General principles of how these redox reactions are catalyzed are becoming lucid as the reactions are modeled theoretically and experimentally. Proton and CO2 reduction and the generation of C-C bonds from simple precursors are important reactions in industry. H2 could be the clean fuel of the future. Hopefully, the knowledge gained from studies of hydrogenase, CO dehydrogenase, and acetyl-CoA synthase can be used to improve life on earth.

Aldehyde Oxidoreductases↗

PubMed1991

What might echography learn from image science?

We review the current state of knowledge of the processes by which the information content of ultrasonic pulse-echo images is transferred to an observer, to the point of contributing to diagnostic judgments. As systematic knowledge in this specific field is rather sparse, we present relevant information and techniques derived from other areas of image science, both medical and otherwise. Quantitative measures both of the information content of ultrasonic and other images and of their characteristic noise content are first considered. An account is then given of the relevant aspects of human visual psychophysics, with particular reference to perception of contrast and detail, image texture, movement and colour, again with emphasis on documenting quantitative aspects of such behaviour. Against this background, we consider the efficiency, in current practice, of image information transfer to a human observer, how and to what extent this could be improved by changes in practice and, in particular, in what situations substantial innovations in machine processing of image data would be expected to improve human performance. It is suggested that several problems in the field may provide a worthwhile and challenging scope for future research.

Humans↗

PubMedDate not supplied

Telecommunications and nursing education.

Telecommunications are becoming increasingly important to nursing educators. At the University of Nebraska Medical Center College of Nursing, communication by two-way television, computers, facsimile machines, and telephone conferences is essential to the administration and operation of a school with four divisions located across 500 miles. Two-way television is available through one system that uses satellite and fiberoptic technology and another that uses telephone lines. The four campuses of the college share classes, administrative meetings, and conferences through television. Faculty members teaching via TV are oriented to designing instructional material for transmission and to the minor quirks of the technology. Students in TV classes must be aware of their responsibility for active involvement in learning. Studies have found no significant differences in the grades of students in "live" classrooms and those in TV classrooms, but both faculty and students prefer the face-to-face situation. The College of Nursing uses computers extensively on an internal network linking the four campuses for E-mail, file transfer, computer-assisted instruction, and administrative information sharing. Another computer network, Synapse Health Resources Online, links the college and the Medical Center with health professionals in rural areas throughout the state.

Academic Medical Centers↗

PubMed1998

How to interpret an anonymous bacterial genome: machine learning approach to gene identification.

In this report we address the problem of accurate statistical modeling of DNA sequences, either coding or noncoding, for a bacterial species whose genome (or a large portion) was sequenced but not yet characterized experimentally. Availability of these models is critical for successful solution of the genome annotation task by statistical methods of gene finding. We present the method, GeneMark-Genesis, which learns the parameters of Markov models of protein-coding and noncoding regions from anonymous bacterial genomic sequence. These models are subsequently used in the GeneMark and GeneMark.hmm gene-finding programs. Although there is basically one model of a noncoding region for a given genome, several models of protein-coding region are automatically obtained by GeneMark-Genesis. The diversity of protein-coding models reflects the diversity of oligonucleotide compositions, particularly the diversity of codon usage strategies observed in genes from one and the same genome. In the simplest and the most important case, there are just two gene models-typical and atypical ones. We show that the atypical model allows one to predict genes that escape identification by the typical model. Many genes predicted by the atypical model appear to be horizontally transferred genes. The early versions of GeneMark-Genesis were used for annotating the genomes of Methanoccocus jannaschii and Helicobacter pylori. We report the results of accuracy testing of the full-scale version of GeneMark-Genesis on 10 completely sequenced bacterial genomes. Interestingly, the GeneMark.hmm program that employed the typical and atypical models defined by GeneMark-Genesis was able to predict 683 new atypical genes with 176 of them confirmed by similarity search.

Algorithms↗

PubMed2026

Integrative multi-omics and single-cell analysis identifies EGFR pathway activation and metabolic reprogramming as potential synthetic lethal vulnerabilities in resistance to the FGFR inhibitor AZD4547.

BACKGROUND: Although fibroblast growth factor receptor (FGFR) inhibitors (FGFRi) have demonstrated clinical promise, the inevitable emergence of acquired resistance remains a critical bottleneck, severely compromising their long-term clinical efficacy. The pan-cancer molecular landscape and heterogeneous mechanisms driving this resistance, ranging from genetic alterations to dynamic network rewiring, remain poorly understood. METHODS: We integrated large-scale pharmacogenomic profiling of the FGFR inhibitor AZD4547 from the GDSC2 and PRISM databases with single-cell RNA sequencing to dissect the multi-omics landscape of FGFRi resistance across 312 cell lines from 8 cancer types. This multi-omics framework was further extended by machine learning modeling and systematic synthetic lethality screening to uncover actionable therapeutic targets. In vitro viability assays and western blot analysis were subsequently conducted to experimentally evaluate the predicted FGFR-EGFR synthetic lethality. RESULTS: Our dual-database analysis unveiled a multi-dimensional atlas of FGFRi resistance. We identified cancer-specific genomic drivers, such as ELF4 amplification in glioblastoma, alongside key transcriptomic markers including UCP2 and FSCN1, highlighting a shift towards metabolic reprogramming and epithelial-mesenchymal transition (EMT). Single-cell analysis unveiled that resistance is linked to the heterogeneous enrichment of baseline subpopulations characterized by distinct metaprograms, including cell-cycle dysregulation. Furthermore, a random forest model built on a LASSO-derived transcriptomic signature was constructed, demonstrating promising predictive capability for AZD4547 sensitivity (mean test-set AUC = 0.73, 95% CI [0.63, 0.80]); the signature generalized well to erdafitinib but showed limited transferability to some other FGFR inhibitors (e.g. pemigatinib, BGJ398). Most notably, our synthetic lethal screening revealed a convergent reliance on compensatory RTK signaling (specifically EGFR pathway enrichment) and downstream MAPK/PI3K cascades in resistant phenotypes, providing converging computational evidence for EGFR pathway activation as an adaptive bypass mechanism. This predicted synthetic lethality was experimentally supported in two FGFR-dependent cell line models (RT112 and CCLP1), in which combined FGFR-EGFR inhibition produced marked synergistic antiproliferative effects. CONCLUSIONS: This study establishes a comprehensive multi-omics atlas of resistance to the FGFR inhibitor AZD4547, delineating convergent mechanisms of metabolic reprogramming and EGFR-mediated bypass signaling. Our findings characterize the resistance as a dynamic network rewiring and nominate rational combination strategies to overcome this therapeutic bottleneck. While FGFR-EGFR co-inhibition is experimentally supported, metabolic co-targeting remains a computationally derived, hypothesis-generating strategy.

Benzamides↗

PubMed2025

Common to rare transfer learning (CORAL) enables inference and prediction for a quarter million rare Malagasy arthropods.

DNA-based biodiversity surveys result in massive-scale data, including up to millions of species-of which, most are rare. Making the most of such data for inference and prediction requires modeling approaches that can relate species occurrences to environmental and spatial predictors, while incorporating information about their taxonomic or phylogenetic placement. Even if the scalability of joint species distribution models to large communities has greatly advanced, incorporating hundreds of thousands of species has not been feasible to date, leading to compromised analyses. Here we present a 'common to rare transfer learning' (CORAL) approach, based on borrowing information from the common species to enable statistically and computationally efficient modeling of both common and rare species. We illustrate that CORAL leads to much improved prediction and inference in the context of DNA metabarcoding data from Madagascar, comprising 255,188 arthropod species detected in 2,874 samples.

Animals↗

PubMed1987

Carola, a computer system for automatic documentation in anesthesia.

A computer system has been designed for documentation and data acquisition during open heart surgery. This computer system (called 'Carola') processes all patient data during cardiac surgery. More than 50 analogue or digital signals are scanned. These are derived from a monitoring rack, a Siemens Servo 900B ventilator with its accessory devices and a heart lung machine. All these values are plotted as well as offline data, such as medications, fluids, laboratory results and user comments, on an A3 format anesthetic record using an eight pen flat bed plotter. Simultaneously all data is written onto a cassette tape. These tapes are then transferred to a database for storage and statistical processing. The sampling frequency is every 10 seconds, averages being calculated over one minute periods. The chart is updated once a minute normally or every 15 minutes for slowly changing signals e.g. temperatures. Hardware and software of the computer have modular design. The hardware consists of two Motorola 6809 based microprocessor systems. The software is entirely written in Pascal. The user interface is implemented on a menu driven basis. A terminal with a keyboard is used for the communication with the users, namely anesthetic nurses and anesthesiologists. The system was readily accepted by the users. The menu structure proved to be easy to learn and allowed fast entries, even when the users were not previously accustomed to the use of a keyboard. The clear and detailed presentation of the data on the plotted chart helped to detect trends early and facilitated therapeutic decisions. From december 1983 the first prototype was used on a routine basis, followed by a second unit in June 1984 and a third in December 1985. Up to now more than 12.500 anesthetic hours have been recorded. Since then almost 100% of all anesthetics performed in our cardiothoracic unit have been documented by the computers, including all short procedures without invasive monitoring and all emergencies.

Anesthesiology↗

PubMedDate not supplied

[Difficulties of describing human relationships with the help of psychoanalytic descriptive models: a critique of ego-psychology].

Progress of psychotherapy and of related behaviour sciences makes evident the importance of a better understanding of human relations. But psychoanalysis finds it hard to describe interpersonal processes without transference. In order to remain within the conceptional frame of metapsychology it has to see interaction between individuals as the oral, aggressive or sexual cathexis of an object or as satisfaction or denial of the subject by the object. The structure of the "ego", which--in analogy to medical thinking--is conceived as an organ with its functions, is considered to have no interpersonal activities. The "ego" of the classic psychoanalytic theory is chiefly occupied with itself. It has to care for its egoistical interests and to guarantee its self-preservation. As an auxiliary and meanwhile popular concept the "self" has been introduced to describe object-relations. This concept is not sharply defined. Due to its metapsychological implications it produces additional theoretical difficulties. Linguistic studies show that every inventory of words implies a certain insight into reality. For this reason the metapsychological machine-like concept of psychic structures does not permit new ideas about interpersonal relations. If we leave metapsychology and base on colloquial speech we see that the experience of "I" is much more related to persons than the rather autistic concept of the "ego" shows. Further we learn that self-preservation cannot be an egoistical interest; it depends on the attachment to others. All feelings of self-esteem depend much more on interpersonal relations than on "narcissistic regulations". From these experiences three conclusions are derived: a) One of the main qualities of the ego is the relatedness to persons. b) The concept of narcissistic regulation as a successor of primary narcissism is no longer useful. Narcissistic traits develop as the secundary compensations if the individual failed to build up satisfactory interpersonal relations. c) The revision of (a) ego-psychology and (b) theory of narcissism asks for modifications of the therapeutic technique, where now the interest is especially concentrated on interpersonal problems instead on the pathology of the ego.

Drive↗

PubMedDate not supplied

The AcCell series 2000 as a support system for training and evaluation in educational and clinical settings.

Providing effective training, retraining and evaluation programs, including proficiency testing programs, for cytoprofessionals is a challenge shared by many academic and clinical educators internationally. In cytopathology the quality of training has immediately transferable and critically important impacts on satisfactory performance in the clinical setting. Well-designed interactive computer-assisted instruction and testing programs have been shown to enhance initial learning and to reinforce factual and conceptual knowledge. Computer systems designed not only to promote diagnostic accuracy but to integrate and streamline work flow in clinical service settings are candidates for educational adaptation. The AcCell 2000 system, designed as a diagnostic screening support system, offers technology that is adaptable to educational needs during basic and in-service training as well as testing of screening proficiency in both locator and identification skills. We describe the considerations, approaches and applications of the AcCell 2000 system in education programs for both training and evaluation of gynecologic diagnostic screening proficiency.

Automation↗

PubMed1996

Toward a new outlook on primate learning and behavior: complex learning and emergent processes in comparative perspective.

Primate research of the 20th century has established the validity of Darwin's postulation of psychological as well as biological continuity between humans and other primates, notably the great apes. Its data make clear that Descartes' view of animals as unfeeling "beast-machines" is invalid and should be discarded. Traditional behavioristic frameworks--that emphasize the concepts of stimulus, response, and reinforcement and an "empty-organism" psychology--are in need of major revisions. Revised frameworks should incorporate the fact that, in contrast to the lifeless databases of the "hard" sciences, the database of psychology entails properties novel to life and its attendant phenomena. The contributions of research this century, achieved by field and laboratory researchers from around the world, have been substantial--indeed revolutionary. It is time to celebrate the progress of our field, to anticipate its significance, and to emphasize conservation of primates in their natural habitats.

Animals↗

PubMed2004

Predicting the efficiency of UAG translational stop signal through studies of physicochemical properties of its composite mono- and dinucleotides.

In this study, we explored the problem of predicting the UAG stop-codon read-through efficiency. The reported nucleotide sequences were first converted into physicochemical property vectors before being presented to a machine learning algorithm. Two sets of physicochemical properties were applied: one for mononucleosides (in terms of steric bulk, hydrophobicity and electronics) and another for dinucleotides. To the best of our knowledge, this is the first report of how dinucleotides are converted into principle components derived from NMR chemical shift data. A few efficiency prediction models were then derived and a comparison between mononucleoside and dinucleotide-based models was shown. In the derived models, the coefficients of these property based predictors lend themselves to bio-physical interpretations, an advantage which is demonstrated in this study via a prediction model based on the steric bulk factor. Although it is quite simple, the steric bulk factor model explained well the effect of sequence variations surrounding the amber stop codon and the tRNA bearing UCCU anticodon. We further proposed new alternatives at position -1 and +4 of a UAG stop codon sequence to enhance the readthrough efficiency. This research may contribute to a better understanding of the readthrough mechanisms and may also help to study the normal translation termination process.

Codon, Terminator↗

PubMed2001

Comparison of video trainer and virtual reality training systems on acquisition of laparoscopic skills.

Training on a video trainer or computer-based minimally invasive surgery trainer leads to improved benchtop laparoscopic skill. Recently, improved operative performance from practice on a video trainer was reported. The purpose of this study was three fold: (a) to compare psychomotor skill improvement after training on a virtual reality (VR) system with that after training on a video-trainer, (VT) (b) to evaluate whether skills learned on the one training system are transferable to the other, and (c) to evaluate whether VR or VT training improves operative performance. For the study, 50 junior surgery residents completed baseline skill testing on both the VR and VT systems. These subjects then were randomized to either a VR or VT structured training group. After practice, the subjects were tested again on their VR and VT skills. To assess the effect of practice on operative performance, all second-year residents (n = 19) were evaluated on their operative performance during a laparoscopic cholecystectomy before and after skill training. Data are expressed as percentage of improvement in mean score/time. Analysis was performed by Student's paired t-test. The VR training group showed improvement of 54% on the VR posttest, as compared with 55% improvement by the VT group. The VR training group improved more on the VT posttest tasks (36%) than the VT training group improved on the VR posttest tasks (17%) (p <0.05). Operative performance improved only in the VR training group (p <0.05). Psychomotor skills improve after training on both VR and VT, and skills may be transferable. Furthermore, training on a minimally invasive surgery trainer, virtual reality system may improve operative performance during laparoscopic cholecystectomy.

Animals↗

PubMed2006

Construct and face validity and task workload for laparoscopic camera navigation: virtual reality versus videotrainer systems at the SAGES Learning Center.

BACKGROUND: Laparoscopic camera navigation (LCN) training on simulators has demonstrated transferability to actual operations, but no comparative data exist. The objective of this study was to compare the construct and face validity, as well as workload, of two previously validated virtual reality (VR) and videotrainer (VT) systems. METHODS: Attendees (n = 90) of the SAGES 2005 Learning Center performed two repetitions on both VR (EndoTower) and VT (Tulane Trainer) LCN systems using 30 degrees laparoscopes and completed a questionnaire regarding demographics, simulator characteristics, and task workload. Construct validity was determined by comparing the performance scores of subjects with various levels of experience according to five parameters and face validity according to eight. The validated NASA-TLX questionnaire that rates the mental, physical, and temporal demand of a task as well as the performance, effort, and frustration of the subject was used for workload measurement. RESULTS: Construct validity was demonstrated for both simulators according to the number of basic laparoscopic cases (p = 0.005), number of advanced cases (p < 0.001), and frequency of angled scope use (p < 0.001), and only for VT according to training level (p < 0.001) and fellowship training (p = 0.008). Face validity ratings on a 1-20 scale averaged 15.4 +/- 3 for VR vs. 16 +/- 2.6 for VT (p = 0.04). Ninety-six percent of participants rated both simulators as valid educational tools. The NASA-TLX overall workload score was 69.5 +/- 24 for VR vs. 68.8 +/- 20.5 for VT (p = 0.31). CONCLUSIONS: This is the largest study to date that compares two validated LCN simulators. While subtle differences exist, both VR and VT simulators demonstrated excellent construct validity, good face validity, and acceptable workload parameters. These systems thus represent useful training devices and should be widely used to improve surgical performance.

Adult↗