Multi-step Transition Research Articles

Educating the pediatrician of the 21st century: defining and implementing a competency-based system.

The final product of the Accreditation Council for Graduate Medical Education (ACGME) Outcomes Project is to improve health care through ensuring the competence of physicians during their training and beyond. Its success depends on a paradigm shift to a competency-based model of medical education. This article presents an overview of the model and describes the first stages of this multistep transition in a university setting. Our hope is to raise awareness of the impact on the pediatric community at large and provide a foundation on which other educators can continue to build. The ACGME established 6 domains of competence as the first step in the paradigm shift. To begin work on the second step of establishing benchmarks for evaluation of competence and thresholds at which they should be achieved, the educational leadership from the primary care departments formed a work group with the support of a Health Resources and Services Administration grant. Review of the literature led us to embark on a stepwise process for initiating a competency-based system of medical education. We established the benchmarks by a process of individual effort followed by group consensus. These benchmarks, in the aggregate, permit an evaluator to determine whether a given competency has been achieved. The next phases of step 2 required setting thresholds for the demonstration of competence and finally establishing consensus regarding the threshold for competence at each level of training for each specific benchmark. To accomplish the latter, we surveyed the program directors of the 202 accredited pediatric training programs that are members of the Association of Pediatric Program Directors. Eighty-one members (40%) completed our survey. Although some controversy existed for thresholds during the postgraduate-year-1 level, majority consensus was reached for nearly all benchmarks at the upper levels of training. Impact of the shift to competencies for medical students and practicing physicians is also reviewed. Having defined the benchmarks and thresholds for the 6 ACGME domains of competence, we are well positioned to move to step 3: developing the necessary tools to evaluate competence. The move to competency-based education impacts the entire pediatric community. Lessons learned from our experience may be generalized and thus be of value to the community at large.

Microstrip lateral RF MEMS switch integrated with multistep CPW transition

A new type of microstrip lateral metal-contacting micro-electromechanical systems (MEMS) series switch using an enhanced transition-design technology is proposed and demonstrated. It uses a conductor-backed coplanar waveguide (CBCPW) connected to a microstrip back-to-back MEMS transmission line without any via holes or bonded wires. The RF measurements of this switch show an off-state isolation of 18 dB and an on-state insertion loss of less than 2 dB at 6–27 GHz. In addition, the simplicity of this fabrication process is achieved using deep reactive-ion etching (DRIE), micromachining technology, and silicon-on-insulator (SOI) substrate. © 2004 Wiley Periodicals, Inc. Microwave Opt Technol Lett 44: 93–95, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.20557

Magnetic properties of TbPdSn single crystal

Abstract The thermal variation of magnetic susceptibility of the orthorhombic TbPdSn single crystal indicates a successive magnetic transition at T N =23.8 K, T 1 =12.2 K and T 2 =2.5 K. The magnetization along the b -axis exhibits a multi-step metamagnetic transition in the three ordered phases. The easy axis of magnetization is the b -axis as in other isoastructural Tb ternary compounds of TbNiSn and TbRhGe. A comparison is made for the CEF parameters in these three Tb compounds.

Multistep phase transition induced by CO 2 adsorption observed in a novel microporous medium based upon 1-D coordination polymer: [Cu(II) 2(O 2CPh) 4(2,5-dmpyz)] n

A novel crystalline solid, [Cu(II) 2(O 2CPh) 4(2,5-dmpyz)] n (2,5-dmpyz = 2,5-dimethyl-pyrazine), was synthesized and characterized by single-crystal X-ray diffraction analysis. The compound demonstrates multistep phase transition induced by CO 2 adsorption, which readily obeys the Clausius– Clapeyron equation in terms of the set of partial pressures of CO 2 and transition temperatures.

Thermal hysteresis phenomena and mesoscopic phase coexistence around the neutral-ionic phase transition in TTF-CA and TMB-TCNQ

Hysteresis phenomena are investigated around the temperature-induced neutral-ionic (N-I) phase transition in the prototype compound tetrathiafulvalene-p chloranil (TFF-CA). A multistep transition is evidenced by neutron scattering, with plateau evolution of Bragg peaks characteristic of symmetry breaking, as well as by specific heat measurements revealing a multipeak structure, both in perfect agreement. A structural study reveals the coexistence of N and I phases at a mesoscopic scale during the thermal hysteresis. No gradual process with intermediate long periodicity structure based on alternating N and I planes, as theoretically suggested, takes place. These results, supported by optical microscopy studies performed on both TTF-CA and tetramethylbenzidine-tetracyanoquinodimethane (TMB-TCNQ) crystals, underline the importance of interstack elastic coupling at the temperature-induced neutral-ionic transition.

Fourier transform infrared spectroscopy suggests unfolding of loop structures precedes complete unfolding of pig citrate synthase.

Pig citrate synthase (PCS) can be used as a model enzyme to gain some insight into the structural basis of protein thermostability. The thermal unfolding characteristics of the specific secondary structure elements within PCS were monitored in detail by following changes in its amide I band components. The result of our study indicates that PCS undergoes irreversible thermal denaturation. Detailed analysis reveals that the different secondary structures display a multistep transition with a major and a minor transition at different temperatures and a very small initial transition at the same temperature (30 degrees C). A plot of temperature-induced changes in (1)H-(2)H exchange, the decrease in the absorbance of the alpha-helical structures, and the increase in the absorbance of aggregated structures all have in common a multistep transition, the minor one centered at 45 degrees C and the major one around 59 degrees C. In contrast, a band that is tentatively assigned to loop structures displays these same minor and major transitions but at lower temperatures (39 and 52 degrees C, respectively). The transition, which occurs at 39-45 degrees C, is not associated with the appearance of aggregated structures. This transition may reflect a change in the tertiary structure of the protein. However, the final transition, which occurs at a higher temperature (52-59 degrees C), reflects unfolding and aggregation of the polypeptide chains. The Fourier transform infrared (FTIR) analysis suggests that PCS has a thermolabile region that unfolds first, some 7 degrees C below the main unfolding of the protein. We propose that this reflects the unfolding of the highly flexible loop segments, which in turn triggers the unfolding of the predominantly helical core structure of PCS.

Mechanisms for the multistep spin reorientation of ultrathin Fe films on Gd

The multistep spin reorientation transition of ultrathin iron films on bulk gadolinium is described theoretically. We find that it is necessary to include cubic terms in the magnetic anisotropy energy expansion in order to explain this phenomenon. Furthermore, the signs of the anisotropy coefficients required to explain the coexistence of both first- and second-order phase transitions in this spin reorientation transition are obtained. We can then model this system using either a surface or a bulk driven model, or a combination of both.

Heterogeneous genetic alterations in ovarian mucinous tumors: Application and usefulness of laser capture microdissection

Histologic observation of ovarian mucinous tumors suggests that there is a multistep transition through the accumulation of genetic alterations. We analyzed loss of heterozygosity (LOH) and replication error (RER) on TP53 and D17S855 as well as K-ras point mutations of the heterogeneous histologic areas of the same tumor in 26 cases of ovarian mucinous tumor. The laser capture microdissection (LCM) technique has been applied to the study of K-ras point mutation in 10 cases. As for genetic alterations for LOH or RER on TP53 and D17S855, 2 (1 borderline tumor and 1 carcinoma) of 14 cases and 4 (1 borderline tumor and 3 carcinomas) of 12 cases, respectively, showed genetic heterogeneities in different histologic areas. Six (2 borderline tumors and 4 carcinomas) of 18 cases showed heterogeneity of K-ras point mutation in the different histologic areas of the same tumor, and 5 (1 cystadenoma with Brenner tumor component, 2 borderline tumors, and 2 carcinomas) of 10 cases showed heterogeneous K-ras mutation pattern in the same tumor when the LCM technique was used. Atypical areas tended to show K-ras point mutations frequently. Out of 3 cases of mixed mucinous cystadenoma and Brenner tumor, 1 case showed K-ras point mutation in the Brenner tumor area but not in the area of mucinous cystadenoma. These preliminary results suggest that a subset of ovarian mucinous tumors occur through multistep carcinogenesis and show that LCM is useful for molecular pathologic studies. HUM PATHOL 32:1203-1208. Copyright © 2001 by W.B. Saunders Company

Synthesis and Characterization of Multiresponsive Core−Shell Microgels

We report the synthesis and characterization of temperature and pH responsive hydrogel particles (microgels) with core−shell morphologies. Core particles composed of cross-linked poly(N-isopropylacrylamide) (p-NIPAm) or poly(NIPAm-co-acrylic acid) (p-NIPAm-AAc) were synthesized via precipitation polymerization and then used as nuclei for subsequent polymerization of p-NIPAm-AAc and p-NIPAm, respectively. The presence of a core−shell morphology was confirmed by transmission electron microscopy (TEM). Thermally initiated volume phase transitions were interrogated via temperature-programmed photon correlation spectroscopy (TP-PCS) as a function of solution pH. The p-NIPAm-AAc core hydrogel displays both a strong temperature and pH dependence on swelling. However, both p-NIPAm-AAc (core)/p-NIPAm (shell) and p-NIPAm (core)/p-NIPAm-AAc (shell) particles display a more complex pH dependence than the homogeneous particles. Specifically, a multistep volume phase transition appears when the AAc component becomes hi...

Unusual magnetic and transport properties of layered compound Gd 0.925La 0.075Mn 2Ge 2

In the layered compound Gd 0.925La 0.075Mn 2Ge 2, a reentrant ferrimagnetism having a para-( T C)-ferri-( T t1)-antiferro-( T t2)-ferri transition with decreasing temperature was observed. Between T t1 and T t2, a field-induced matamagnetism from collinear antiferromagnetism to ferrimagnetism appears, accompanied with a multi-step transition, the so-called “devil's stair-case”. In addition, a giant magnetoresistance effect (Δ ρ/ ρ∼15%) was also observed at the metamagnetic transition. These unusual features will be characteristic in layered antiferromagnetism.

Smooth muscle-specific SM22 protein is expressed in the adventitial cells of balloon-injured rabbit carotid artery.

During the "response-to-injury" process after a mechanical insult to the porcine coronary arteries, the adventitial cells acquire the structural characteristics of myofibroblasts before being incorporated into smooth muscle (SM) layer. We assessed whether the SM-specific SM22 protein can be used as a tracer of adventitial cell-myofibroblast differentiation in the mild balloon injury of rabbit carotid artery. To achieve this goal, we used 2 monoclonal anti-SM22 antibodies (E-11 and 1-B8) and a molecular probe for the SM22alpha mRNA isoform in immunocytochemical and in situ hybridization experiments. The differentiation profile and the migratory and proliferative ability of activated adventitial cells were evaluated by a panel of antibodies to some SM and nonmuscle antigens and pulse- and end-labeling with bromo-deoxyuridine, respectively. In adventitial cells, SM22 antigenicity and SM22alpha mRNA were detectable at days 2 and 4 and, to a lesser extent, at days 7 and 21 after injury, particularly near the adventitia-media interface and mostly colocalizing with bromo-deoxyuridine-positive cells. The pulse-labeling experiments showed that the large majority of these cells penetrated the outermost layer of the tunica media without migrating to the subendothelial region. The phenotypic features of activated migrating and nonmigrating adventitial cells resembled those of vimentin-actin myofibroblast subtype and fetal-type SM cells. These findings indicate that a direct exposure of adventitia to the lumen is not required for phenotypic changes and proliferation/migration of these cells. After comparison of the SM22 expression in arterial vessels during early stages of development, we hypothesize that in the injured carotid artery the mural incorporation of adventitial cells and the spatiotemporal activation of SM22 expression are reminiscent of the vascular morphogenetic process and suggest the existence of a stem cell-like reservoir in adventitia. The early adventitial upregulation of SM22 expression in the injured vessel might be related to a multistep transition process in which nonmuscle cells are converted to myofibroblasts and, possibly, to SM cells.

Kinks motion and underdamped dc-driven dynamics of atomic monolayers

A multi-step dynamical phase transition from the locked to the running state of atoms in response to a dc external force is studied by molecular dynamics simulations of the generalized Frenkel-Kontorova models in the underdamped limit. We show that the hierarchy of depinning transition recently reported [Braun et al., Phys. Rev. Lett. 78 (1997) 1295] strongly depends on the friction. In the present study we consider (i) a generalized FK model with highly anisotropic quasi-one-dimensional rectangular potential, and (ii) an isotropic triangular system, where the interactions between neighboring “channels” play an important role in the dynamics.

Magnetic Field Effect on Laser Isotope Separation Based on Polarization Selection Rules

Excitation dynamics of atoms by linearly polarized lasers were analyzed for J=2→2→1→0 multistep transition under a magnetic field. The time evolution of the population in each magnetic substate was calculated by solving the rate equations under the condition where the atomic alignment is gradually destroyed by the precession motion of the angular momentum around the magnetic field. Isotopic selectivity in the laser isotope separation based on the polarization selection rules was discussed. It has been found that a relatively small magnetic field may cause a degradation of selectivity in the case of Gd and the magnetic field should be kept as small as the terrestrial magnetic field when the laser polarization is perpendicular to the magnetic field.

Is the System Dynamics Society ready for virtual proceedings: some empirical findings and recommendations for action

As methods of publishing documents have moved from paper to a wide variety of electronic formats, the publication policies of the System Dynamics Society have also changed from full-text paper proceedings to a mix of paper abstracts, and CD-ROM and Web-based full-text documents. These changes have been instituted not only to facilitate access to documents, but also to save the considerable cost of publishing full-text volumes for conferences. Interview research at the 1997 System Dynamics Conference in Istanbul, Turkey looked at participants' access to and use of electronic information technologies for full-text conference articles. Interviewees reported lack of technology, insufficient knowledge about technologies, lack of professional incentives, and institutional demands as barriers to the use of strictly paperless dissemination of information. The Society will need to consider a multi-step transition to electronic proceedings, serving as an educator as well as clarifying the roles of the proceedings and the journal for dissemination of differing sorts of information about research in this field. Although it seems clear that the future lies in electronic communication, the speed and method of getting there need careful consideration. © 1998 John Wiley & Sons, Ltd.

Dynamical phase diagram of the dc-driven underdamped Frenkel-Kontorova chain

Multistep dynamical phase transition from the locked to the running state of atoms in response to a dc external force is studied by MD simulations of the generalized Frenkel-Kontorova model in the underdamped limit. We show that the hierarchy of transition recently reported [Braun et al, Phys. Rev. Lett. 78, 1295 (1997)] strongly depends on the value of the friction constant. A simple phenomenological explanation for the friction dependence of the various critical forces separating intermediate regimes is given.

Thermal road for fullerene annealing

The Stone-Wales transformation has been proposed as a basic process for ring rearrangement in a fullerene cage and, consequently, for annealing fullerene structures down to the ground state. We present a new, thermally activated, mechanism for the Stone-Wales transformation. This mechanism, found in dynamical simulations of C 60, involves a multi-step isomerization transition process in contrast with the commonly assumed single-step mechanism. The step-to-step energy barriers found in the multistep process are much lower than the reported ones for single-setp process. We also present a dynamical simulation of the thermal fullerene-to-graphite reconstruction of C 60 of relevance to the growth of fullerenes. The two thermal processes presented open new roads for investigating the formation and annealing mechanisms of different carbon structures.

THE STUDIES ON MULTIPLE METASTABLE STATES IN MAGNETIC MULTILAYER

Using a classical approach, the magnetic configuration of ground state has been studied for the ferromagnetic multilayer system with easy axis anisotropy. The existence of multiple metastable states are obviously shown, and a multi-step transition is presented in the magnetic loop of hysteresis. A bilayer system is discussed analytically, and the numerical calculations are carried out for some complicated multilayer systems.

Spontaneous reformation of the intramolecular thioester in complement protein C3 and low temperature capture of a conformational intermediate capable of reformation.

Three human plasma proteins contain intramolecular thioester bonds: complement components C3 and C4 and alpha 2-macroglobulin. Their thioesters form when glutamine and cysteine residues react in the newly translated proteins and ammonia is released. We have reversed this reaction by treating C3 with ammonia to cleave the thioester and reform the original Gln and Cys. Thioester scission initiates a multistep conformational transition. One intermediate was sufficiently stable to be isolated by high performance liquid chromatography. It lacked native C3 functions and was shown to contain one free sulfhydryl group. Incubation of this ammonia-inactivated C3 intermediate in the absence of ammonia resulted in refolding to a native C3 conformation and recovery of thioester-dependent functions, as evidenced by: 1) return of hemolytic function, 2) return of autolytic cleavage of the alpha-chain, and 3) return of the ability to attach to surfaces during complement activation. Refolding and thioester reformation were dependent on a free SH group and were inhibited by HgCl2 and other thiol-specific reagents. Incubation of ammonia-inactivated C3 at 25 degrees C at pH 7.4 resulted in recovery of 70% of the original C3 function. Refolding and thioester reformation exhibited a Gibbs free energy of +5.2 kcal/mol and were favored over unfolding to the final inactive form. During reformation of native C3 from 14CH3NH2-treated C3, return of the native conformation was accompanied by release of radiolabel from the protein and return of hemolytic complement function. These results suggest that folding of C3 provides both the energy and environment necessary to react the Gln and Cys residues, release ammonia, and form the thioester bond.

Obligatory wounding requirement for tumorigenesis in v-jun transgenic mice

Avian sarcoma virus 17 induces fibrosarcomas in chickens and can transform a number of avian cell types in vitro by the action of v-jun. This gene and the related cellular genes c-jun, jun B and jun D, encode transactivating (or repressing) DNA-binding proteins that form homo- or heterodimeric (Jun-Jun and Jun-Fos) complexes which recognize the AP-1 consensus sequence TGACTCA, a response element that confers sensitivity to the tumour-promoting phorbol ester TPA. We have produced several lines of transgenic mice carrying the v-jun oncogene, driven by the promoter of the widely expressed H-2KK major histocompatibility complex (MHC) class I antigen gene. Transgenic animals are initially phenotypically normal, but after full-thickness wounding they show abnormal wound repair, characterized by hyperplastic granulation tissue. Many of these lesions are slowly progressive because of continuing fibroblast proliferation, and over 2-5 months some give rise to dermal fibrosarcomas. This reproducible multistep transition through a proliferative but benign intermediate is associated with characteristic increments in v-jun expression. Moreover, hyperplastic wound repair and its progression are both related to transgene dosage, suggesting that there exists a quantitative requirement or threshold for v-jun action. Our results indicate that v-jun is not oncogenic in transgenic mice as a result of a 'single-hit' mechanism, but rather, in addition to an obligatory wound, that secondary genetic or epigenetic events (possibly conscripting normal constituents of wound repair) are necessary for tumour development and progression.

Physicochemical characterization of alpha-crystallins from bovine lenses: hydrodynamic and conformational properties.

A detailed investigation of hydrodynamic and conformational behavior has been made of the HM alpha-crystallin and alpha-crystallins of bovine lens. Results from this study indicated that HM alpha (high-molecular-weight alpha-crystallin) and alpha (low-molecular-weight alpha-crystallin) possess considerable size and charge heterogeneities in their native structures and subunit polypeptides, respectively. Sedimentation velocity showed a heterogeneous polydisperse system of HM alpha with an average sedimentation coefficient of about 50S and a more homogeneous system of alpha-crystallin of 20 S. Viscosity and circular dichroism studies pointed to a compact and globular shape of dominant beta-sheet conformation for alpha-crystallin, yet a highly asymmetrical and aggregated form for HM alpha. The conformational stability of alpha-crystallin was investigated in the presence of various denaturants. The evidence presented shows that hydrogen bonding is the main force in maintaining the quaternary structure of compact native alpha-crystallin. Conformational flexibility of alpha-crystallin demonstrated in the equilibrium unfolding study indicated a multistep transition that made the extraction of thermodynamic data from the heat denaturation study difficult. Temperature perturbation on alpha-crystallin suggested the possible involvement of hydrophobic interaction in the aggregation process, leading to the formation of HM alpha from alpha-crystallin. The comparison of conformational properties between HM alpha and alpha-crystallin strongly indicated that HM alpha is a denatured form of alpha-crystallin.