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[KMFTR (Kotz Modular Femur Tibia Reconstruction System) modular tumor endoprosthesis system for the lower extremity].

206 patients with tumorendoprosteses of the KMFTR-type at the lower extremity were operated at the Institute Rizolli Bologna and at the University Clinic of Vienna. The minimum follow up was 2 years (mean 3.2, max. 8 years). In order to bridge the defect caused by tumor resection the proximal femur was replaced in 42 cases, the distal femur in 119 cases and in 6 patients a total femur prosthesis was used. The proximal tibia was replaced in 35 cases and in 4 cases a total knee prosthesis was implanted. Clinical evaluation according to Enneking revealed 71.6% excellent and good results. In 83.4% the radiological score was higher then 20. We saw deep infections in 8.2% (17 patients), breakage of the prosthesis in 6.8% and aseptic loosening in 5.8%. 3 patients had to be amputated due to infection. In the remaining cases of infection in 66% of the patients healing was observed. All cases of aseptic loosening or breakage could be revised successfully by an exchange of the prostheses and therefore salvage of the leg was achieved.

Adolescent

Dissociation of modular hip arthroplasty components after dislocation. A report of three cases at differing dissociation levels.

Modular hip arthroplasty systems, currently widely employed, offer the advantage of increased intraoperative flexibility in component selection with reduced inventory, as well as the disadvantage of modular component dissociation. Dissociation during closed reduction for dislocation is reported in three patients at three different interface levels: (1) fixed acetabular shell-polyethylene linear interface, (2) bipolar acetabular component-femoral head interface, and (3) femoral head-neck interface. Subsequent open reduction was required in each case. Although this potential disadvantage of modular hip systems does not outweigh the benefits, it does warrant that certain precautions be taken when implanting modular components. The acetabular linear should lie flush within the metallic shell after impaction. The femoral head should be firmly impacted onto the neck. Both should resist reasonable manual force of disassembly. Should a modular hip arthroplasty component dislocate, gentle reduction under general anesthesia and fluoroscopic control is warranted. Careful inspection of pre- and postreduction roentgenograms for signs of modular component dissociation is mandatory.

Adult

Mechanisms of failure of modular prostheses.

The expectations of wear and longevity of total hip components are based in large part on Charnley's early work. The evolution of the total hip from the one-piece, all-polyethylene acetabular component and fixed-head femoral component to the myriad of parts that comprise many of today's total hip designs has brought with it an array of potential mechanisms for failure that were not present in the earlier design. The risk/benefit ratio of these new designs may need to be reevaluated based on the additional mechanisms for failure that they provide. One hundred eleven acetabular hip prostheses and 139 femoral prostheses, all of modular configuration, retrieved by surgeons in the field, and sent for histologic examination, were analyzed for this study. A number of component characteristics were found to be correlated to early failure. These included acetabular designs with thin polyethylene bearings, poor fixation of the polyethylene to the metal shell, and geometries that permitted a moment to be applied to the bearing insert, tending to cause it to rotate in the metal shell. Modular femoral components were observed to be susceptible to corrosion, with titanium-alloy stems mated to cast cobalt-alloy heads at greatest risk attributable to a galvanic effect. All modular connections of femoral and acetabular components are at risk for disassociation and fretting; therefore, clever design and precision machining are necessary to produce prostheses in which the benefits of modularity exceed the risks.

Acetabulum

Modular expression and secretion vectors for Bacillus subtilis.

A modular vector system has been developed for the extracellular production of heterologous proteins in Bacillus subtilis. This modular vector system consists of four secretion vectors which are based upon the genes encoding the Bacillus amyloliquefaciens extracellular alkaline protease, neutral protease, barnase and levansucrase. The modular vectors contain compatible restriction sites downstream from the signal peptide-coding region. Three reporter proteins (staphylococcal protein A, levansucrase and Escherichia coli alkaline phosphatase) that offer complementary advantages for cloning, genetic manipulations and media optimization have been fused to the various signal peptides. These secretion vectors function in E. coli and hence can be used to compare the mechanisms of protein secretion in E. coli and B. subtilis.

Alkaline Phosphatase

A rational design of synthetic peptide vaccine with a built-in adjuvant. A modular approach for unambiguity.

We describe a peptide vaccine model containing a built-in adjuvant. This model used a multiple antigen peptide system (MAPS) to amplify peptide antigens and a lipoamino acid, tripalmitoyl glyceryl cysteine (P3C), as a built-in adjuvant. An 18-residue peptide antigen (B2) derived from the third variable domain (amino acid 312-329) of the glycoprotein gp120 of type I human immunodeficiency virus (HIV-1) was used in this model. This peptide antigen is a suitable target since it consists of neutralizing, T-helper, and T-cytotoxic epitopes. The peptide antigen in a tetravalent MAPS format (B2M-P3C) with a lipophilic attachment was synthesized by two routes for comparison: a direct stepwise approach and an indirect modular approach. In the stepwise approach, each residue was sequentially added to the peptide resin to give B2M-P3C and the P3C was incorporated to the side chain of a carboxyl terminal lysine as Fmoc-Lys(P3C). In the modular approach, a module containing a chloroacetylated core matrix of MAPS (M-P3C) with a carboxyl tetrapeptide bearing Lys(P3C) and a second module containing the peptide antigen B2 with a cysteine at its terminus were synthesized and purified separately, and then coupled to each other to form B2M-P3C. In the modular approach, the molecular ion of B2M-P3C was unambiguously identified by ion-spray mass spectrometry. B2M-P3C, administered in liposomes without any adjuvant such as Freund's complete adjuvant, was used to immunize mice and found to induce gp120-specific antibodies in vitro, and prime cytotoxic T lymphocytes in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Vaccines

[Experience with modular system tumor prostheses].

Authors elaborated a modular tumor prosthesis by the use of which the bone segment lost after the resection of hip, femur, knee and proximal tibial tumors can be supplemented in the desired measure. The components of the prosthesis set and the field of its use are described. In the last one and half year modular tumor prostheses were inserted in 10 patients: in 6 primary bone tumors and 4 solitary metastases. One shoulder, 5 hip, 3 stiff knee and 1 tibia diaphysis supplementing modular prostheses were inserted. In spite of 2 complications the initial experiences are encouraging, and in adequate indication the possibility of retaining limb and articular function beside good functional results is given.

Bone Neoplasms

Genomically integrated cassettes swapping: bringing modularity to the strain level in Saccharomyces cerevisiae.

A large variety of synthetic biology toolkits for the introduction of multiple expression cassettes is available for Saccharomyces cerevisiae. Unfortunately, none of these tools is designed to allow the modification - exchange or removal - of the cassettes already integrated into the genome in a standardized way. The application of the modularity principle therefore ends to the steps preceding the final host engineering, making microbial cell factories construction stiff and strictly sequential. In this work, we describe a system that easily allows CRISPR-mediated swapping or removal of previously integrated cassettes, thus bringing the modularity to the strain level, enhancing the possibility of modifying existing strains with a reduced number of steps. In the system, each cassette is tagged with specific barcodes, which can be used as targets for CRISPR nucleases (Cas9 and Cas12a), allowing the excision of the construct from the genome and its substitution with another expression cassette or the restoration of the wild type locus in one single standardized step. The system has been applied to the previously developed Easy-MISE toolkit and tested by swapping fluorescent protein expression cassettes with an efficiency of ∼90% quantified by PCR and flow cytometry.

Saccharomyces cerevisiae

Modular transposition and the dynamical structure of eukaryote regulatory evolution.

This paper examines a model in which transposable elements provide a modular architecture for the cellular genome, complemented by cellular recombinational transformations, arising in turn as a dynamical consequence of this modular structure. It is proposed that the ecology of transposable elements in a given organism is a function of recombinational protocols of the evolving cellular genome. In mammals this is proposed to involve coordinated meiosis-phased activation of LINEs, SINEs and retrogenes complemented by endogenous retroviral transfer between cells.

Animals

Modular structure of the FixL protein of Rhizobium meliloti.

FixL protein of Rhizobium meliloti is a haemo-protein kinase which activates the transcription of nifA and fixK genes via the transcriptional activator protein FixJ under microaerobic conditions. FixL and FixJ proteins belong to the family of two-component regulatory systems for which primary sequence data predicts a modular structure. We showed, using Escherichia coli as heterologous host, that FixL indeed has a modular structure. The amino-terminal hydrophobic domain is dispensable for the oxygen-regulated activity of FixL in vivo. The central cytoplasmic non-conserved domain is necessary for the oxygen-sensing function of FixL whereas it is not necessary for the activation of FixJ by FixL. We propose that, under aerobic conditions, the central domain represses the activating function associated with the carboxy-terminal conserved domain.

Bacterial Proteins

Vibrissaeless mutant rats with a modular representation of innervated sinus hair follicles in the cerebral cortex.

Specialized areas in the cerebral cortex are essential to mediate the various sensory modalities and are crucial to their recovery in disease. We recently observed that prenatal photoreceptor cues are not indispensable for the development of the elaborate modular organization of the primate primary visual (striate) cortex (Kuljis, R. O. and P. Rakic. 1990. Proc. Natl. Acad. Sci. USA 87: 5303-5306). By contrast, the elegant experiments of Woolsey, Van der Loos, and collaborators (Van der Loos, H., and T. A. Woolsey. 1973. Science 179: 395-398; Van der Loos, H. and J. Dörfl. 1978. Neurosci Lett. 7: 23-30; Woolsey, T. A. 1967. John Hopkins Med. J. 121: 91-112; Woolsey, T. A. and H. Van der Loos. 1970. Brain Res. 17: 205-242) indicate that postnatal vibrissal receptor input is necessary for the development of modular organization in the posteromedial barrel subfield (PMBSF) of the rodent somatosensory cortex. The present report is part of a series of studies designed to address the variables that result in seemingly different results in these two models. Here, I address the role of pre- and postnatal tactile experience in the development of the rat homologue of the mouse PMBSF using mutants that lack vibrissae. Mutants exhibit cytoarchitectonic units in layer IV similar to those in controls, as revealed by NissI stains and histochemistry for succinate dehydrogenase and cytochrome oxidase. Sections from flat mounts of the vibrissal pad reveal that all mutants contain vibrissal follicles with stumps of sinus hairs in a geometric array and number similar to that in controls, and that the follicles are innervated heavily by fascicles of fibers from the infraorbital nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Modular Formula: an approach to management of infants with specific or complex food intolerances.

Modular Formula is a dietary preparation for use in treating infants with complex malabsorptive disorders and for weaning infants from total parenteral nutrition. With this formula the physician can alter the quality of the various nutrients normally fed to infants as well as concentrations of those nutrients. Infants who cannot tolerate existing proprietary formulas will often thrive with the judicious use of this flexible formula. Modular Formula provides the clinician with a useful aid in the diagnosis and treatment of chronic diarrhea of infancy.

Diarrhea, Infantile

Modular integrated fluidized bed bioreactor technology.

We describe the design and demonstrate the application of a modular integrated fluidized bed bioreactor system. Basically the system is a reactor vessel equipped with an extending cylinder and a liquid distributor plate. Instead of an external recirculation loop, as used in existing fluidized bed systems, a low shear stress impeller is used as the recirculation pump. The system has several unique features, such as modular exchangeable elements, efficient oxygenation and the option of operating as a stirred tank-, a packed bed- or a fluidized bed reactor. An example of a fluidized bed run using CHO-K1 cells is shown. Under standard culture conditions a 100-fold increase in cell density (up to 1.2 x 10(8) cells/ml) was achieved.

Animals

The Denver universal microspectroradiometer (DUM). II. Computer configuration and modular programming for radiometry.

This paper describes and discusses for microscopists and spectroscopists the choice of computer equipment and the design of programs used in the Denver Universal Microspectroradiometer (DUM). This instrument is an accurate computerized photon-counting microspectrophotometer, microspectrofluorimeter and microrefractometer. The computer is used to control the operation of the system, to acquire radiometric data of various kinds, and to reduce, analyse and output the data in a readily usable form. Since the radiometer was designed to carry out many kinds of measurements in a variety of micro- and macroscopic specimens, and since different methods of microscopy or spectroscopy have to be combined in various ways fro the study of any one specimen, no single master-program could fulfill efficiently all foreseeable requirements. Therefore, the programming developed is interactive, modular, hierarchical and hybrid. Modular interactive programming makes it possible for almost any kind of main program, applicable to almost any kind of measurement, to be assembled quickly from a collection of hierarchical subroutines. Main programs are short and composed mainly of Fortran statements calling subroutines; subroutines, in turn, automatically call other subroutines over many levels. The subroutines are independently written and optimized for maximum operational efficiency in the computer system used, or for maximum ease of transfer to other systems. This approach to programming enables someone unfamiliar with computer languages to operate the radiometric system from the console of the CRT terminal. The writing of new main programs, by linking groups of existing subroutines, requires only a minimum acquaintance with Fortran; only the writing and revision of subroutines requires programming experience. Differences and similarities in the method of computer operation between the present system and other computerized radiometers are briefly discussed.

Computers

Modularization of the type II secretion gene cluster from Xanthomonas euvesicatoria facilitates the identification of a structurally conserved XpsCLM assembly platform complex.

Many bacterial pathogens depend on a type II secretion (T2S) system to secrete virulence factors from the periplasm into the extracellular milieu. T2S systems consist of an outer membrane secretin channel, a periplasmic pseudopilus and an inner membrane-associated assembly platform including a cytoplasmic ATPase. The components of T2S systems are often conserved in different bacterial species, however, the architecture of the assembly platform is largely unknown. Here, we analysed predicted assembly platform components of the Xps-T2S system from the plant-pathogenic bacterium Xanthomonas euvesicatoria. To facilitate these studies, we generated a modular xps-T2S gene cluster by Golden Gate assembly of single promoter and gene fragments. The modular design allowed the efficient deletion and replacement of T2S genes and the insertion of reporter fusions. Mutant approaches as well as interaction and crosslinking studies showed that the predicted assembly platform components XpsC, XpsL and XpsM form a trimeric complex which is essential for T2S and associates with the cytoplasmic ATPase XpsE and the secretin XpsD. Structural modeling revealed a similar trimeric architecture of XpsCLM homologs from Pseudomonas, Vibrio and Klebsiella species, despite overall low amino acid sequence similarities. In X. euvesicatoria, crosslinking and fluorescence microscopy studies showed that the formation of the XpsCLM complex is independent of the secretin and vice versa, suggesting that the assembly of the T2S system is a dynamic process which involves the association of preformed subcomplexes.

Xanthomonas

Modular hemiarthroplasty for fractures of the proximal part of the humerus.

A new biomodular prosthesis was used for the treatment of a displaced fracture of the proximal part of the humerus in twenty-two shoulders in twenty-two patients. The fractures were classified according to the Neer system; there were thirteen four-part, five three-part, and four head-splitting fractures. There were fifteen women and seven men, and the mean age was seventy years (range, forty-nine to eighty-seven years). The hemiarthroplasty was performed an average of eleven days (range, one to forty-five days) after the injury. The deltopectoral interval was used in all patients, and the prosthesis was implanted with cement in twenty of the shoulders. All of the patients participated in a supervised program of rehabilitation. The patients were followed for an average of thirty-six months (range, twenty-six to forty-nine months). Twenty of the twenty-two patients had a good or excellent result. The active forward elevation averaged 119 degrees; external rotation, 40 degrees; and internal rotation, to the twelfth thoracic vertebra. All of the patients except for the two who had a poor result had satisfactory relief of pain. The two patients who had a poor result had a successful revision with a modular prosthesis of the same design. The modular head could be removed, enabling the surgeon to gain access to the glenoid and to adjust the soft tissues. The over-all scores correlated inversely with the age of the patients and the interval from the injury to the operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

[Modular way of sampling for determination of the degree of occupational exposure at industrial plants with periodically changing dust concentration].

A work station with dustiness changing periodically during a workshift is one of the most common types of work stations, as regards exposure dynamics. Cyclic significant concentrations of dust occurring from time to time result from a specific technological treatment used. The measuring module will be the time of measurement, starting with the beginning of the cycle of working out a given detail or--the technological process through the whole treating and technological process as well as breaks--due to various reasons--until starting another, analogous operation. What was found is that average dust concentrations obtained from modular measurements correspond to average concentration to which an employee is exposed during the whole workshift. Modular measurements allow to reconstruct work conditions inducing silicosis, and may be helpful in settling the maximum allowable concentration.

Air Pollutants

Systematic modular engineering of genome-integrated Escherichia coli MG1655 for high-level 2'-fucosyllactose production.

2'-Fucosyllactose (2'-FL), the most abundant human milk oligosaccharide (HMO), has attracted considerable interest for its prebiotic and immunomodulatory functions, with broad applications in infant nutrition. In this study, we report the development of a high-yield, genome-integrated 2'-FL-producing strain based on Escherichia coli MG1655 through systematic modular optimization. Starting from a single-copy BKHT strain (MGC06), we first optimized the copy number of the α-1,2-fucosyltransferase (α-1,2-FT) gene BKHT. Subsequently, the GDP-L-fucose supply was enhanced through coordinated genomic integration of the gene clusters cpsG-cpsB and gmd-fcl, while the multidrug efflux transporter gene mdfA was integrated to improve product export and strain robustness. BKHT copy number was then re-evaluated in the optimized background, with four copies yielding the highest production. The final engineered strain, harboring all genetic modifications stably integrated into the chromosome, produced 17.18 g/L 2'-FL in shake-flask culture. In fed-batch fermentation using a 5-L bioreactor, this strain achieved a titer of 154.12 g/L after 60 h, with a productivity of 2.57 g/L/h. Notably, throughout the entire fermentation process, no antibiotics or inducers were supplemented, underscoring the genetic stability and regulatory compliance of this plasmid-free system. To our knowledge, this represents the highest 2'-FL titer reported to date, positioning our engineered strain as a promising candidate for commercial 2'-FL production.

Escherichia coli