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PubMed1996

Modular prostheses in metastatic bone disease of the proximal femur.

In the period from 1988 to 1992, 23 patients (16 females and 7 males, average age at operation 57.3 years) with metastatic disease of the proximal femur were treated by resection of the lesion and insertion of a modular prosthesis (PGR). At latest review (at an average 3.2 years following the operation, range 1 to 5 years) twelve patients were still alive. Local recurrence of the neoplasia occurred at, respectively 6, 8, and 12 months after prosthesis insertion in the three patients in whom surgery was performed because of a pathological fracture. Pain relief was obtained in all cases after surgery and no patient developed any complication during or after surgery. Functional results (Enneking Function Evaluation system) were excellent in 2 patients, good in 13 and fair in 8. PGR modular prostheses appear to be a safe form of palliative treatment in a patient with proximal femoral metastases.

Adult↗
PubMed1996

A modular time-shortened RN to BSN program.

This paper discusses an innovative 16-month, modular baccalaureate nursing program for working associate degree and diploma nursing graduates. This writing-intensive program is grounded in adult and experiential learning theories and consists of 3 components: modules, a practicum project, and a portfolio. Ten modules are taught in a workshop format once a week for 4 hours. The practicum project is a practice-relevant endeavor based on planned change theory. Students work on their project throughout the program. A portfolio is developed by each student. The first cohort of 14 registered nurses is halfway through the modular program. Growth in writing and critical thinking is evident.

Adult↗
PubMed1996

Modularity in total knee arthroplasty.

A prospective study was performed of 41 consecutive revisions using a modular total knee arthroplasty design. The Hospital for Special Surgery knee score improved from 52 +/- 16 preoperatively, to 85 +/- 8 at last evaluation. At last evaluation, the HSS knee scores were excellent in 26, good in 14, fair in 1, and poor in 0 knees. The Knee Society pain score improved from 38 +/- 23 preoperatively to 91 +/- 8 at last evaluation. The Knee Society function score improved from 40 +/- 24 preoperatively to 68 +/- 28 at last evaluation. Incomplete radiolucent lines were seen adjacent to 61% of the components, but not adjacent to the long stems. The results were similar with either pressed fit or cemented long stems or posterior cruciate retaining or posterior stabilized articulations of the prosthetic design. Modularity facilitates revision total knee arthroplasty.

Aged↗
PubMed1997

Modular organization of occipito-temporal pathways: cortical connections between visual area 4 and visual area 2 and posterior inferotemporal ventral area in macaque monkeys.

The modular organization of cortical pathways linking visual area 4 (V4) with occipital visual area 2 (V2) and inferotemporal posterior inferotemporal ventral area (PITv) was investigated through an analysis of the patterns of retrogradely labeled cell bodies after injections of tracers into V4 and PITv. Although cytochrome oxidase or other stains have failed to yield reliable independent anatomical markers for cortical modules beyond V1 and V2, V4 and PITv seem to have modular compartments with specific patterns of cortico-cortical connectivity. Tracer injections of V4 labeled cells in V2 (1) thin stripes exclusively, (2) interstripes exclusively, or (3) specific combinations of interstripe and thin stripe subcompartments. These labeling patterns suggest (1) that there is a complicated organization of inputs to V4, (2) that projections from V2 to V4 display a submodular selectivity, and (3) that projections from V2 to V4 display some degree of cross-stream convergence. Consistent with this framework, extensive regions of PITv provide feedback projections to interstripe-recipient portions of V4, whereas more restricted portions of PITv provide feedback to thin stripe-recipient portions of V4. Similarly, the feedforward projection from V4 to PITv often arose from multiple cell clusters across a wide expanse of V4. When distinguishable fluorescent tracers were injected into two PITv sites separated by 3-5 mm, a variety of projection patterns was observed in V4. In most cases, labeled cells were found in multiple, interdigitating, nonoverlapping clusters of 1-3 mm width, whereas in other cases the two labeled fields were highly intermixed. These results suggest that V4 and PITv contain functional modules that can be characterized by the specific patterns of segregated and convergent projections they receive from lower cortical areas. These specific patterns of intercortical input, in conjunction with intrinsic cortical circuitry, may endow extrastriate cortical neurons with new and more complex receptive field properties.

Animals↗
PubMed1997

[Modularity of prostheses].

Modularity allows a large choice of implants, like the use of cementless acetabular cups inducing bone ingrowth. The length and direction of the neck may also be adapted to be new joint. Risks of modularity are: implant dissociation, restriction of joint mobility, and especially augmentation of metal debris as a potential source of polyethylene wear. It is then critical to play attention to implant design, material choice and planning of the arthroplasty.

Hip Prosthesis↗
PubMed2026

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↗
PubMed1997

The second visual area in the marmoset monkey: visuotopic organisation, magnification factors, architectonical boundaries, and modularity.

The organisation of the second visual area (V2) in marmoset monkeys was studied by means of extracellular recordings of responses to visual stimulation and examination of myelin- and cytochrome oxidase-stained sections. Area V2 forms a continuous cortical belt of variable width (1-2 mm adjacent to the foveal representation of V1, and 3-3.5 mm near the midline and on the tentorial surface) bordering V1 on the lateral, dorsal, medial, and tentorial surfaces of the occipital lobe. The total surface area of V2 is approximately 100 mm2, or about 50% of the surface area of V1 in the same individuals. In each hemisphere, the receptive fields of V2 neurones cover the entire contralateral visual hemifield, forming an ordered visuotopic representation. As in other simians, the dorsal and ventral halves of V2 represent the lower and upper contralateral quadrants, respectively, with little invasion of the ipsilateral hemifield. The representation of the vertical meridian forms the caudal border of V2, with V1, whereas a field discontinuity approximately coincident with the horizontal meridian forms the rostral border of V2, with other visually responsive areas. The bridge of cortex connecting dorsal and ventral V2 contains neurones with receptive fields centred within 1 degree of the centre of the fovea. The visuotopy, size, shape and location of V2 show little variation among individuals. Analysis of cortical magnification factor (CMF) revealed that the V2 map of the visual field is highly anisotropic: for any given eccentricity, the CMF is approximately twice as large in the dimension parallel to the V1/V2 border as it is perpendicular to this border. Moreover, comparison of V2 and V1 in the same individuals demonstrated that the representation of the central visual field is emphasised in V2, relative to V1. Approximately half of the surface area of V2 is dedicated to the representation of the central 5 degrees of the visual field. Calculations based on the CMF, receptive field scatter, and receptive field size revealed that the point-image size measured parallel to the V1/V2 border (2-3 mm) equals the width of a full cycle of cytochrome oxidase stripes in V2, suggesting a close correspondence between physiological and anatomical estimates of the dimensions of modular components in this area.

Animals↗
PubMed1998

Topography of modular subunits in the mushroom bodies of the cockroach.

The mushroom body (MB), a conspicuous neuropil structure in the insect brain, is implicated in associative memory and in some aspects of motor control. Intrinsic neurons of the MB (Kenyon cells) extend dendrites into the calyx, and their axons run through the pedunculus and then bifurcate to form the alpha and the beta lobes. At the pedunculus and the lobes, Kenyon cells make synaptic connections with dendrites of extrinsic (output) neurons. Previously, we reported that the alpha lobe of the cockroach MB consists of repetitive modular subunits (Mizunami et al. [1997] Neurosci. Lett. 229:153-156). Each subunit is composed of a dark layer and a light layer, and the layers are refereed to as slabs. Each slab is composed of axons of a specific subset of Kenyon cells. In the present study, we examined serial sections of reduced silver preparations and found that each dark and light slab continues throughout the length of the pedunculus and the alpha and beta lobes. We also found that Golgi-impregnated Kenyon cells often exhibit a characteristic grouping, forming a thin sheet interlaced by dozens or hundreds of axons. The sheet is much thinner than the slab, and each sheet remains within a particular slab throughout the length of the pedunculus and the lobes. Thus, the sheet is a component forming the slab. In the pedunculus and the beta lobe, a class of Golgi-impregnated extrinsic neurons exhibit segmented dendritelike arbors that interact with every other slab, i.e., either with only dark or light slabs. Because each neuron of this class interacts with each particular set of dark or light slabs, we conclude that the slabs are units for transmitting output signals from the MB.

Animal Structures↗
PubMed1998

New modular delivery system for diagnostic and therapeutic pre-targeting using tautomer-specific monoclonal antibody EM-6-47 and 3-substituted adenines.

We have developed a new modular affinity system for the 2-step delivery of functional molecules to target cells. The system is based on the tautomer-specific monoclonal antibody (MAb) EM-6-47, which binds to 3- and 3,8-substituted adenines with high affinity (Ka > 10(9) l/mol) without cross-reacting with naturally occurring purine derivatives. This MAb serves as the hapten-specific fusion partner to produce bispecific MAbs (bs-MAbs) recognizing a target cell antigen and a low-m.w. hapten as carrier molecule for, e.g., radionuclides. Either the C-8 or the N-3 position of adenines can be used for conjugation with effector molecules; the remaining position may be substituted with different moieties to modulate the pharmacokinetics of the haptens. Different 3- and 3,8-substituted adenines conjugated to the chelates DOTA and DTPA or to the drug daunomycin were synthesized. Adenine-chelate derivatives were efficiently labeled with (111)In and 90Y, while high-affinity binding of 3-substituted adenines to MAb EM-6-47 remained almost unaffected by the conjugation to radiochelates. To confirm the validity of the delivery system, a prototype bs-MAb, EM-168-47, was generated by somatic cell fusion of MAb EM-6-47 and MAb EM-168-2, the latter recognizing a surface antigen on canine hematopoietic cells. Two-step targeting assays in vitro verified the bs-MAb-mediated, dose-dependent delivery of (111)In-labeled adenine-chelate derivatives to myeloid cells. This system represents a powerful tool for new pre-targeting approaches relying on bs-MAbs and low-m.w. haptens. Suitable cellular antigens can be targeted by fusing the appropriate MAbs with hapten-specific MAb EM-6-47, and tailor-made 3-substituted adenines may be labeled with diagnostic or therapeutic radionuclides, cytotoxic drugs or other functional molecules.

Adenine↗
PubMed1998

Risks and advantages in standardization of bores and cones for heads in modular hip prostheses.

Standardization of bores and cones for modular hip prosthesis heads has been addressed by both the International Standard Organisation (ISO) and the American Society for Testing and Materials (ASTM) in response to the need to control the conditions of head-trunnion fit that thereby improves implant safety. Standardization of these conditions could help the surgeon avoid fit mismatch, especially during revision surgery. Instituting a system of standardization without taking all critical parameters into consideration, however, could be more dangerous than no system at all. The current article discusses the main taper parameters that directly influence the performance of ceramic head-metallic trunnion assemblies and argue for standardization that integrates all these parameters. Several examples, based on experimental mechanical tests and finite element analysis, are given to support the argument.

Equipment Design↗
PubMed1996

Modular elements of the MLC 1f/3f locus confer fiber-specific transcription regulation in transgenic mice.

The two proteins encoded by the fast alkali myosin light chain (MLC) 1f/3f locus are developmentally regulated, muscle specific, and expressed exclusively in fast-twitch fibers. Their expression is independently regulated by two separate promoters and a downstream enhancer. Previous studies showed a reporter gene directed by the rat MLC If promoter and MLC enhancer to exhibit correct skeletal muscle-specific expression in transgenic mice during development and to be preferentially expressed in fast-twitch Type IIB fibers [Donoghue et al., (1991) J. Cell B.ol. 115:423-434]. The MLC 3f promoter also directed muscle-specific expression of a CAT reporter gene in adult transgenic mice and showed little dependence upon the enhancer. Here, we show that the MLC 3f promoter also directs transgene expression in the fast-twitch fibers of adult skeletal muscle, but almost exclusively to fiber Types IIA and IIX. MLC 3f transgene expression occurs in only a subset of the fiber types that express the endogenous locus, indicating modular elements included in the transgene confer fiber-specific transcription regulation. MyoD protein was also found to be restricted to fiber Types IIA and IIX, providing evidence for its possible role in mediating fiber-specific gene expression.

Animals↗
PubMed1999

Modular gradient coil: A new concept in high-performance whole-body gradient coil design.

A new concept in high-performance MR gradient coil design is presented which we have called the Modular Gradient Coil (MGC). This novel design approach results in an actively shielded whole-body gradient coil containing multiple and independent elements, integrated onto a single former, for generating gradient fields along each of the three axes (x, y, and z). These elements can be energized in a number of configurations, using a single gradient power supply unit (PSU), to generate a whole range of gradient performance levels. The design criteria for the MGC also include a requirement to prohibit peripheral nerve stimulation in all of its modes of operation. This requirement is achieved, while simultaneously providing high performance, by specifying different volumes of gradient linearity for each of the operating modes. Magn Reson Med 42:561-570, 1999.

Biophysical Phenomena↗
PubMed2000

Modular representations of odorants in the glomerular layer of the rat olfactory bulb and the effects of stimulus concentration.

To study the mechanism whereby odorants are encoded in the nervous system, we studied the glomerular-layer activity patterns in the rat olfactory bulb evoked by closely related odorants from different chemical families. These odorants had a common straight-chain hydrocarbon structure, but differed systematically in their functional groups. Neural activity was mapped across the entire glomerular layer by using the ¿(14)C2-deoxyglucose method. Group responses were averaged and compared by using data matrices. The glomerular activity patterns that resulted from this analysis were comprised of modules. Unique combinations of modules were activated by each odorant, demonstrating what may be part of the neural code for odorants. Most of the modules were clustered together in the bulb, perhaps providing for enhanced contrast between related chemicals by means of lateral inhibition. We also determined whether changes in odorant concentration would affect spatial patterns of glomerular activity. Two odorants, pentanal and 2-hexanone, evoked different patterns at increased concentrations, with additional glomeruli being recruited at a great distance from glomeruli in which activity was evoked at lower concentrations. Humans report that both of these odorants change in perceived odor with increasing concentration. Three other odorants (pentanoic acid, methyl pentanoate, and pentanol) did not recruit new areas of glomerular activation with increasing concentration, and humans do not report a changed odor across concentrations of these odorants. The results suggest that changes in modular glomerular activity patterns could underlie altered odor perception across odorant concentrations, and they provide additional support for a combinatorial, spatially based code in the olfactory system.

Animals↗
PubMed2000

A modular approach to structurally diverse bidentate chelate ligands for transition metal catalysis

A modular approach to a new class of structurally diverse bidentate P/N, P/P, P/S, and P/Se chelate ligands has been developed. Starting from hydroquinone, various ligands were synthesized in a divergent manner via orthogonally bis-protected bromohydroquinones as the central building block. The first donor functionality (L1) is introduced to the aromatic (hydroquinone) ligand backbone either by Pd-catalyzed cross-coupling (Suzuki coupling) with hetero-aryl bromides, by Pd-catalyzed amination, or by lithiation and subsequent treatment with electrophiles (e.g., chlorophosphanes, disulfides, diselenides, or carbamoyl chlorides). After selective deprotection, the second ligand tooth (L2) is attached by reaction of the phenolic OH functionality with a chlorophosphane, a chlorophosphite, or a related reagent. Some of the resulting chelate ligands were converted into the respective PdX2 complexes (X = Cl, I), two of which were characterized by X-ray crystallography. The methodology developed opens an access to a broad variety of new chiral and achiral transition metal complexes and is generally suited for the solid-phase synthesis of combinatorial libraries, as will be reported separately.

Journal Article↗
PubMed2001

Chiral modular n-butyllithium aggregates: nbuli complexes with anisyl fencholates.

Chiral, enantiopure aggregates are formed spontaneously by mixing solutions of n-butyllithium with anisyl fenchols. X-ray crystal analyses reveal the structures of these aggregates with different ortho substituents in the anisyl moieties (X), X = H (1-H), SiMe3 (2-H), tBu (3-H) SiMe2(tBu) (4-H) and Me (5-H). While the complex of 1-BuLi shows a 3:1 composition, 2-BuLi, 3-BuLi and 4-BuLi yield 2:2 stoichiometries. The aggregate 5-BuLi crystallizes with a 2:4 composition and hence is a derivative of hexameric n-butyllithium, in which two trans-situated nBuLi molecules are substituted by lithium fencholate moieties. The variety in the synthesized chiral nBuLi aggregates demonstrates the high propensity of anisyl fencholates to chirally modify nBuLi. Variations in the modular ligand structures by alterations of the ortho-substituents (X) enable tunings of compositions and also of enantioselectivities in nBuLi additions to benzaldehyde.

Journal Article↗
PubMed2025

Modular Photoswitchable Molecular Glues for Chemo-Optogenetic Control of Protein Function in Living Cells.

Optogenetic systems using photosensitive proteins and chemically induced dimerization/proximity (CID/CIP) approaches enabled by chemical dimerizers (also termed molecular glues), are powerful tools to elucidate the dynamics of biological systems and to dissect complex biological regulatory networks. Here, we report a versatile chemo-optogenetic system using modular, photoswitchable molecular glues (sMGs) that can undergo repeated cycles of optical control to switch protein function on and off. We use molecular dynamics (MD) simulations to rationally design the sMGs and further expand their scope by incorporating different photoswitches, resulting in sMGs with customizable properties. We demonstrate that this system can be used to reversibly control protein localization, organelle positioning, protein-fragment complementation as well as posttranslational protein levels by light with high spatiotemporal precision. This system enables sophisticated optical manipulation of cellular processes and thus opens up a new avenue for chemo-optogenetics.

Optogenetics↗
PubMed2002

The Modular Resource Center: integrated units for the study of the anatomical sciences in a problem-based curriculum.

The Modular Resource Center (MRC) at the College of Veterinary Medicine at Cornell University was created in 1993 as a way to provide visual resources in support of a newly implemented problem-based curriculum in which the anatomical sciences are taught primarily in the first tutorial-based course, The Animal Body. Over two dozen modules have been created specifically in support of this course, whereas additional modules have been created in support of other basic science courses. The basic unit of organization of the MRC is a module presented in a carrel that provides students a way to study, either alone or in groups, a given topic. The topic is presented through a script and an integrated set of anatomical materials including plastinated dissected specimens, vascular casts, skeletal preparations, models, radiographs, histological slides, and photo- and electron micrographs. The key feature of this resource center is that it is not a museum; rather it is more analogous to an interactive library, that can be used for reference, study, and review, not only by veterinary students but also by faculty, interns, residents, and undergraduates. A unique aspect is that all materials have been made by veterinary students working with faculty during the summer. Although started as a resource in support of a tutorial-based curriculum, the MRC has evolved over a decade into an anatomy resource that would be highly valued in any curricular format.

Anatomy↗