Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “modularity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
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↗
PubMed2025

A Versatile Disulfide-Containing Solid-Support Strategy for 3'-Modifiers in Oligonucleotides: Introducing Modular Tandem Oligonucleotide Synthesis.

Chemical modifications of oligonucleotides are routinely employed to enhance their functional properties. Amino-modifiers serve as versatile chemical handles for postsynthetic (bio)conjugation, nucleic acid immobilization on solid supports, and investigations into nonenzymatic genome replication relevant to the origins of life, to name a few. Here, we report a cost-effective, disulfide-containing solid-support linkage that enables the on-column synthesis of nucleic acids with 3'-amino or 3'-phosphate modifications. The orthogonality of this solid-support linker facilitates an on-column protecting group strategy, enabling the synthesis of DNA and RNA containing 3'-amino-2',3'-dideoxyribosides from commercial unprotected mononucleosides. Additionally, we present an on-column deprotection protocol for DNA and RNA, prior to cleavage from the solid support, eliminating the precipitation step typically required in conventional RNA workflows, leading to higher recovery for certain strands. Expanding on our previous work, we introduce a versatile modular tandem oligonucleotide synthesis (mTOS) approach, allowing selective release of downstream strands from the one directly bound to the solid-support via the disulfide-containing linker. Together, these advances in solid-support design and oligonucleotide synthesis unlock new opportunities in bioconjugation, biotechnology, and the study of prebiotic replication mechanisms, broadening the utility of chemically modified nucleic acids across research disciplines.

Disulfides↗
PubMedDate not supplied

A modular on-line three-dimensional liquid chromatography-tandem mass spectrometry approach to characterization of organelle proteomes.

In this work we describe the use of a modular multidimensional chromatography-tandem mass spectrometry approach for rapid identification of proteins. In particular we highlight the use of a strong cation exchange cartridge in conjunction with a membrane postconcentration cartridge and nano-HPLC on-line with tandem mass spectrometry to characterize the eosinophil granule organelle proteome. Details are provided of the analytical approach we have developed and we discuss some of the advantages compared with previously reported analyses, as well as providing some specific examples of novel proteins identified.

Amino Acid Sequence↗
PubMed2006

The structural basis for docking in modular polyketide biosynthesis.

Polyketide natural products such as erythromycin and rapamycin are assembled on polyketide synthases (PKSs), which consist of modular sets of catalytic activities distributed across multiple protein subunits. Correct protein-protein interactions among the PKS subunits which are critical to the fidelity of biosynthesis are mediated in part by "docking domains" at the termini of the proteins. The NMR solution structure of a representative docking domain complex from the erythromycin PKS (DEBS) was recently solved, and on this basis it has been proposed that PKS docking is mediated by the formation of an intermolecular four-alpha-helix bundle. Herein, we report the genetic engineering of such a docking domain complex by replacement of specific helical segments and analysis of triketide synthesis by mutant PKSs in vivo. The results of these helix swaps are fully consistent with the model and highlight residues in the docking domains that may be targeted to alter the efficiency or specificity of subunit-subunit docking in hybrid PKSs.

Amino Acid Sequence↗
PubMed2001

Clinical and angiographic performance of a new-generation modular stent design for treatment of de novo coronary lesions.

The objectives of the Race Car study were to assess the safety and efficacy of the Medtronic AVE S670 stent, a new-generation stent with a modular design consisting of interconnected sinusoidal rings allowing improved flexibility with good conformability and scaffolding. A total of 285 stents were implanted in 267 patients with (un)stable angina pectoris who underwent angioplasty of a single de novo lesion in a native coronary artery with a diameter between 3.0 and 4.0 mm. Available stent lengths were 9, 12, and 15 mm. The primary endpoint was the 6-month restenosis rate. Secondary endpoints were device and procedural success and major adverse cardiac event (MACE)-free survival at 1 and 6 months. All patients received the study stents and no other stents were used (angiographic success: 100%). Eight patients experienced a MACE during hospital admission (Q-wave MI in 2, non-Q-wave MI in 4, TLR in 2). A procedural success was obtained in 97% of the patients. There were no additional events at 1 month. The clinical endpoints encountered at 6 months were Q-wave MI in 1, bypass surgery in 3, and repeat angioplasty in 25 (MACE-free survival: 86.5%). Quantitative angiographic results were the minimum lumen diameter increased from 1.05 +/- 0.32 before to 2.73 +/- 0.39 mm after stent implantation. At follow-up, the loss in diameter was 0.74 +/- 0.50 mm. The loss index was 0.45 +/- 0.31 and restenosis rate was 13.4%. This study has demonstrated that the S670 stent in patients with (un)stable angina pectoris requiring intervention of a single lesion has a low acute and 6-month major event rate and a low angiographic restenosis rate.

Aged↗
PubMed2003

Employing the structural diversity of nature: development of modular dipeptide-analogue ligands for ruthenium-catalyzed enantioselective transfer hydrogenation of ketones.

A library of novel dipeptide-analogue ligands based on the combination of tert-butoxycarbonyl(N-Boc)-protected alpha-amino acids and chiral vicinal amino alcohols were prepared. These highly modular ligands were combined with [[RuCl(2)(p-cymene)](2)] and the resulting metal complexes were screened as catalysts for the enantioselective reduction of acetophenone under transfer hydrogenation conditions using 2-propanol as the hydrogen donor. Excellent enantioselectivity of 1-phenylethanol (up to 98 % ee) was achieved with several of the novel catalysts. Although most of the ligands contained two stereocenters, it was demonstrated that the absolute configuration of the product alcohol was determined by the configuration of the amino acid part of the ligand. Employing ligands based on L-amino acids generated S-configured products, and catalysts based on D-amino acids favored the formation of the R-configured alcohol. The combination N-Boc-L-alanine and (R)-phenylglycinol (Boc-L-Ab) or its enantiomer (N-Boc-D-alanine and (S)-phenylglycinol, Boc-D-Aa) proved to be the best ligands for the reduction process. Transfer hydrogenation of a number of aryl alkyl ketones were evaluated and excellent enantioselectivity, up to 96 % ee, was obtained.

Acetophenones↗
PubMed2003

Modular synthesis of heparin oligosaccharides.

A general, modular strategy for the first completely stereoselective synthesis of defined heparin oligosaccharides is described. Six monosaccharide building blocks (four differentially protected glucosamines, one glucuronic and one iduronic acid) were utilized to prepare di- and trisaccharide modules in a fully selective fashion. Installation of the alpha-glucosamine linkage was controlled by placing a conformational constraint on the uronic acid glycosyl acceptors thereby establishing a new concept for stereochemical control. Combination of disaccharide modules to form trans-uronic acid linkages was completely selective by virtue of C2 participating groups. Coupling reactions between disaccharide modules exhibited sequence dependence. While the union of many glucosamine uronic acid disaccharide modules did not meet any problems, certain sequences proved not accessible. Elaboration of glucosamine uronic acid disaccharide building blocks to trisaccharide modules by addition of either one additional glucosamine or uronic acid allowed for stereoselective access to oligosaccharides as demonstrated on the example of a hexasaccharide resembling the ATIII-binding sequence. Final deprotection and sulfation yielded the fully synthetic heparin oligosaccharides.

Antithrombin III↗
PubMed2004

Ligand bite governs enantioselectivity: electronic and steric control in Pd-catalyzed allylic alkylations by modular fenchyl phosphinites (FENOPs).

Modular fenchyl phosphinites (FENOPs) containing different aryl units-phenyl (1), 2-anisyl (2), or 2-pyridyl (3)-are efficiently accessible from (-)-fenchone. For comparison of the influence of the different aryl units on enantioselectivities and reactivities, these FENOPs were employed in Pd-catalyzed allylic alkylations. The strongly chelating character of P,N-bidentate 3 is apparent from X-ray structures with PdCl2 ([Pd3Cl2]), and with allyl-Pd units in ([Pd3(eta1-allyl)] and [Pd3(eta3-allyl)]). FENOP3 gives rise to a PdL* catalyst of moderate enantioselectivity (42 % ee, R product). Surprisingly, higher enantioselectivities are found for the hemilabile, monodentate FENOPs 1 (83 % ee, S enantiomer) and 2 (69 % ee, S enantiomer). Only small amounts of 1 or 2 generate selective PdL* catalysts, while complete abolition of enantioselectivity appears with unselective PdL*2 species with higher FENOP concentrations in the cases of 1 or 2. Computational transition structure analyses reveal steric and electronic origins of enantioselectivities. The nucleophile is electronically guided trans to phosphorus. endo-Allyl arrangements are favored over exo-allyl orientations for 1 and 2 due to Pd-pi-pyridyl interactions with short "side-on" Pd-aryl interactions. More remote "edge-on" Pd-pi-aryl interactions in 3 with Pd-N(lp) coordination favor endo-allyl units slightly more and explain the switch of enantioselectivity from 1 (S) and 2 (S) to 3 (R).

Journal Article↗
PubMed2005

Highly modular synthesis of C1-symmetric aminosulfoximines and their use as ligands in copper-catalyzed asymmetric Mukaiyama-aldol reactions.

The development of C1-symmetric aminosulfoximines, their highly modular synthesis, and their application in enantioselective copper-catalyzed Mukaiyama-type aldol reactions between pyruvates and enolsilanes is described. In this context, the influence of the ligand architecture as well as the optimization of the reaction conditions are discussed. In detail, the dependence of the catalyst efficiency on the solvent, the metal source and the temperature are reported, and an interesting additive effect is highlighted. Furthermore, the substrate scope will be presented. With the optimized catalyst system, a number of aldol products with quaternary stereogenic centers have been obtained in high yields and with enantiomeric excesses up to 99 %.

Journal Article↗
PubMed2006

Modular approach to tridentate N,O,N' ligands using pyrazolylborate chemistry.

Two anionic tridentate N,O,N' chelators, [pz(Ph)B(mu-pz)(mu-O)B(Ph)pz](-) (3(-)) and [pz(Ph)(Ph)B(mu-pz)(mu-O)B(Ph)pz(Ph)](-) (4(-)), as well as the corresponding complexes [Fe(3)(py)Cl], [Fe(3)Cl(2)] and [Cu(3)Cl], have been synthesised and structurally characterised by X-ray crystallography (pz: pyrazolyl, pz(Ph): 3-phenylpyrazolyl, py: pyridine). Since our synthesis approach takes advantage of the highly modular pyrazolylborate chemistry, inexpensive and relatively resistant N,O,N' ligands of varying steric demand are readily accessible. The complexes [Fe(3)(py)Cl] and [Fe(3)Cl(2)] possess a distorted trigonal-bipyramidal configuration with the pyrazolyl rings occupying equatorial positions and the oxygen donor being located at an apical position. The complex [Cu(3)Cl] crystallises as chloro-bridged dimers featuring Cu(II) ions with ligand environments that are intermediate between a square-planar and a trigonal-bipyramidal geometry.

Journal Article↗
PubMed1981

Modular electronics for flow cytometry and sorting: the LACEL system.

LACEL is newly developed, fast, general-purpose data acquisition and processing system for flow cytometric applications. The system's modular electronics allows flexibility in system configurations. The system can process as many as eight input analog parameters and can transfer 16-bit words between the user's electronics and the computer with standard input/output interfaces. The system's 8-fold coincidence logic capability can be set to operate with the noncoincidental timing that may occur in multiparameter flow measurements. As many as four parameters can be used to establish amplitude and timing criteria for each of two sorting directions. Two experiments can be on line with the computer at one time.

Cell Separation↗
PubMed1987

A modular detector for flow cytometric multicolor fluorescence measurements.

A modular detector for measuring multicolor fluorescence from cells illuminated by single or multiple lasers has been developed for flow cytometers. Motion picture projector, camera, and CCTV/video lenses were evaluated for use in the detector by comparing their physical characteristics, image quality, and light collection efficiencies. A 25-mm focal length F/0.95 CCTV lens was selected, based on our criteria and test results. The detector was constructed out of square aluminum extrusion channels. A CCTV lens mounted on the outside of the first channel collected light emitted from cells and collimated it towards filters and secondary CCTV lenses located in each channel. The secondary lenses functioned as relay optics for directing and focusing light onto pinhole spatial filters for measurement by photomultipliers. The detector design allowed any number of channels to be connected together and the versatility for making simultaneous or sequential measurements. Measurements on lymphocytes labeled with four monoclonal antibodies conjugated to fluorescent dyes and measurements on viable tumor cells stained for DNA content and with three fluorescent-labeled antibodies were used to demonstrate the detector's capabilities.

Animals↗
PubMed1993

Kettin, a large modular protein in the Z-disc of insect muscles.

Z-discs of insect flight muscle contain a large protein of 500-700 kDa. Monoclonal antibodies label an epitope in the molecule at the Z-disc in Drosophila and Lethocerus (waterbug). A partial cDNA of 1.6 kb from the Drosophila gene has been cloned and sequenced. The corresponding amino acid sequence has a modular structure composed of four conserved repeats of 95 amino acids homologous to immunoglobulin C2 domains (called class II domains in muscle proteins), separated by less conserved linker sequences of 35 amino acids. An expressed class II domain with flanking linker sequences binds to actin and alpha-actinin but not to myosin. Single molecules of the protein would be large enough to span the Z-disc. We suggest that the protein acts as scaffolding in the Z-disc and we call the protein kettin. The Ca2+ activated protease, calpain, disrupts the Z-disc of striated muscle, releasing alpha-actinin intact. Calpain digests kettin to a series of peptides of between 30 and 170 kDa which are released from the myofibril. Digestion of kettin may cause disintegration of the Z-disc and alpha-actinin release which lead to disassembly of the myofibril.

Amino Acid Sequence↗
PubMed1995

Membrane insertion of the bacterial signal transduction protein ToxR and requirements of transcription activation studied by modular replacement of different protein substructures.

The Vibrio cholerae protein ToxR is an integral membrane protein that acts as a transcription activator in response to environmental signals; it controls expression of toxin genes ctxA and ctxB, along with a variety of other genes related to pathogenicity. Here it is shown that: (i) ToxR has a modular architecture and that activation of transcription starting at the ctx promoter depends strictly on dimerization of the periplasmic ToxR domain; (ii) the transmembrane (TM) region of ToxR is sufficient as a topogenic signal but not for stable membrane anchoring of the protein; (iii) the TM region has no special function in signal transduction and (iv) a proline residue located within the TM region minimizes background transcription activation, most plausibly by reducing TM-TM interaction. Possible applications of ToxR as a technical tool for analysing protein-protein interactions between pairs of arbitrary TM domains are discussed.

ATP-Binding Cassette Transporters↗
PubMed1993

In vivo corrosion of modular hip prosthesis components in mixed and similar metal combinations. The effect of crevice, stress, motion, and alloy coupling.

One hundred forty-eight retrieved modular hip prostheses of both mixed (Ti-6Al-4V/Co-Cr) and similar (Co-Cr/Co-Cr) metal combinations were examined and positive evidence of corrosive attack was found in the conical taper region between head and stem. Significant corrosion was observed in both mixed and similar metal combinations with 16% of necks and 35% of heads (for mixed-metal cases), and 14% of necks and 23% of heads (for similar-metal cases) showing moderate to severe corrosive attack. There was a significant correlation between the percentage of prostheses with moderate to severe corrosion and the duration of implantation for both mixed and similar metal cases, indicating that this corrosion process is progressive in time. Moderate to severe corrosion was seen as early as 2.5 and 11 months (mixed and similar metals, respectively). Scanning electron microscopy and x-ray analysis identified several forms of corrosive attack in the cobalt-based component of the taper. These included, for both mixed and same metal combinations: preferential dissolution of cobalt, fretting, and pitting; mixed metals only: the formation of a Ti-Cr-Mo interfacial phase and interdendritic corrosion; and for similar metals: intergranular attack adjacent to grain boundaries enriched in molybdenum and silicon. It is hypothesized that the restricted crevice environment, coupled with high cyclic stresses which cause repeated fracture of the passive oxide films in the taper, result in an unstable electrochemical environment within the crevice for both the cobalt alloy and Ti-alloy passive films. The passivity of these alloys is subsequently lost and active attack of the taper results. Also, the repeated fracturing of the passive films will result in large amounts of corrosion products being formed. This corrosion and particulate accumulation could result in loss of mechanical integrity of the implants in vivo, create particles for third body wear, and release particles into the surrounding tissues.

Alloys↗
PubMed2001

Homologies of process and modular elements of embryonic construction.

There are several signal transduction pathways that integrate embryonic development. We find that both within species and between species, these pathways constitute homologous modules. The processes, themselves, can be considered homologous, just as structures can be considered homologous. Just like vertebrate limbs, these pathways are composed of homologous parts (in this case, the proteins of the pathway) that are organized in homologous ways. These pathways are conserved through evolutionary time, and they undergo descent with modification. Such homologies of processes become critical to the discussion of evolution and development when we consider (1) that evolution depends on heritable changes in development, (2) that development is modular such that different modules can change without affecting other modules, (3) that modules can be co-opted into new functions, and (4) that modules depend on intercellular communication.

Animals↗
PubMed2004

Craniofacial variability and modularity in macaques and mice.

Evolutionary developmental biology of primates will be driven largely by the developmental biology of the house mouse. Inferences from how known developmental perturbations produce phenotypic effects in model organisms, such as mice, to how the same perturbations would affect craniofacial form in primates must be informed by comparisons of phenotypic variation and variability in mice and the primate species of interest. We use morphometric methods to compare patterns of cranial variability in homologous datasets obtained for two strains of laboratory mice and rhesus macaques. C57BL/6J represents a common genetic background for transgenic models. A/WySnJ mice exhibit altered facial morphology which results from reduction in the growth of the maxillary process during formation of the face. This is relevant to evolutionary changes in facial prognathism in nonhuman primate and human evolution. Rhesus macaques represent a nonhuman primate about which a great deal of phenotypic and genetic information is available. We find significant similarities in covariation patterns between the C57BL/6J mice and macaques. Among-trait variation in genetic and phenotypic variances are fairly concordant among the three groups, but among-trait variation in developmental stability is not. Finally, analysis of modularity based on phenotypic and genetic correlations did not reveal a consistent pattern in the three groups. We discuss the implications of these results for the study of evolutionary developmental biology of primates and outline a research strategy for integrating mouse genomics and developmental biology into this emerging field.

Animals↗
PubMed2004

Modularity and integration in the hominoid scapula.

In this paper, several hypotheses of morphological integration within the hominoid (ape) scapula are tested. In particular, whether the scapula represents a set of developmental tissues sharing tight correlations between constituent parts (i.e., highly integrated) or is more modularly organized (i.e., covariation is greater within regions than between) is tested. Whether the patterns of integration in the scapula have changed over phylogenetic time or in response to selective forces is also examined. Results from two different analyses (matrix correlations and edge deviance) indicate traits comprising the blade and acromion, and to a weaker degree the glenoid, correlate highly with each other. The coracoid exhibits more independence from other parts of the scapula, perhaps reflecting its distinct evolutionary developmental history. Overall, similarity in species-specific patterns of correlation was high between all taxa. Correlation matrix similarity was significantly correlated with functional similarity and morphological distance, but not with phylogenetic distance. These results are congruent with other studies of integration that suggest correlation patterns remain stable over evolutionary time. There are changes associated with phylogeny, but the tight link between functional similarity and phylogenetic distance at this level of comparison presents possible challenges to interpretation. Overall similarities in the pattern of integration in all taxa might be better interpreted as relative strengthening or weakening of trait correlations rather than broadscale changes in the pattern of relationship between developmental regions. Larger sample sizes with greater taxonomic/functional breadth, and finer scale analyses of patterns of correlation are needed to test these hypotheses further.

Animals↗