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Health care delivery requires physicians to operate in teams to successfully navigate complexity in caring for patients and communities. The importance of training physicians early in core concepts of working in teams (i.e., “teaming”) has long been established. Over the past decade, however, little evidence of team effectiveness training for medical students has been available. The recent introduction of health systems science as a third pillar of medical education provides an opportunity to teach and prepare students to work in teams and achieve related core competencies across the medical education continuum and health care delivery settings. Although educators and health care system leaders have emphasized the teaching and learning of team-based care, conceptual models and evidence that inform effective teaming within all aspects of undergraduate medical education (including classroom, clinical, and community settings) are needed to advance the science regarding learning and working in teams. Anchoring teaming through the core foundational theory of team effectiveness and its operational components could catalyze the empirical study of medical student teams, uncover modifiable factors that lead to the evidence for improved student learning, and improve the link among competency-based assessments between undergraduate medical education and graduate medical education. In this article, authors articulate several implications for medical schools through 5 conceptual areas: admissions, the design and teaching of team effectiveness in health systems science curricula, the related competency-based assessments, and course and program evaluations. The authors then discuss the relevance of the measurable components and intended outcomes to team effectiveness in undergraduate medical education as critical to successfully prepare students for teaming in clerkships and eventually residency and clinical practice.

Zusammenfassung: Hintergrund: Die anatomische Darstellung und Erfassung m�glicher Anomalien der Nierengef��e und Ureteren ist f�r die Planung einer Lebendnierenspende von essenzieller Bedeutung. Die vorliegende Untersuchung soll die Wertigkeit der nichtinvasiven Evaluation mit der 64-Zeilen-Multidetektor-CT untersuchen. Material und Methoden: In die Auswertung wurden 63 Lebendnierenspender (LNS) eingeschlossen, die im Zeitraum 12.2004 bis 01.2007 mit der CT pr�operativ untersucht wurden. Die Untersuchungen erfolgten mit einem Somatom-Sensation-Cardiac-64 (Siemens Medical Solutions, Deutschland). Neben einer CT-Angiographie (CTA) wurden eine ven�se Phase des Abdomens und eine Sp�tphase nach 15 min in Low-dose-Technik f�r die CT-Urographie (CTU) durchgef�hrt. Die radiologischen Befunde wurden mit dem intraoperativen Befund oder in 2 F�llen mit der konventionellen Angiographie verglichen, au�erdem wurden Sensitivit�t, Spezifit�t, negativer und positiver Vorhersagewert ermittelt. Ergebnisse: Bei den ausgewerteten 63 LNS (31 weibliche, 32 m�nnliche) erreichte die CTA eine Sensitivit�t von 100% f�r die Arterien und Polarterien und 98,3% f�r die Nierenvenenanatomie. Die Low-dose-CTU erreichte ebenfalls eine Sensitivit�t von 100%. Schlussfolgerung: Die Ergebnisse zeigen, dass eine nichtinvasive pr�operative Planung bei potenziellen Lebendnierenspendern anhand einer 64-Zeilen-Multidetektor-CT im Sinne des „On-stop-Shopping“ zuverl�ssig m�glich ist.

Optimization of proton exchange membrane water electrolyzers (PEMWE) has become a focus of researchers looking for a reliable way to generate power. A vital component to PEMWE operation is the porous transport layer (PTL) on the anode side, which is where oxygen is produced. The PTL must allow water access to the catalyst layer and remove oxygen simultaneously. In this work, a previously developed imaging technique is used to generate bilayer PTL structures. A multiscale modeling approach was used to study the effect of a bilayer PTL on oxygen evolution and PEMWE performance. First, a micro scale model was used to predict oxygen transport pathways through different PTL structures. Results showed that the bilayer PTL results in higher oxygen saturation and faster oxygen transport through the PTL. Second, a macro scale model was used to predict performance using bilayer PTLs. Predictions showed potential values between 10 and 20 mV below single layer potential values. This points to the bilayer improving PEMWE operation. Findings from this work show how the addition of a mesoporous layer to a PTL substrate will improve oxygen transport and removal from the catalyst surface, which will improve PEMWE performance.

Symptoms of inflammatory breast carcinoma include elevated skin temperature, pain, flushing, and edema, which usually occur before a tumor mass is palpable. The prognosis for inflammatory breast carcinoma, which represents two to five percent of breast cancers, is especially poor. The use of chemotherapy has raised the five-year disease-free survival rate to about 40 percent. A combination of chemotherapy and surgery was used to treat 43 patients with nonmetastatic (confined to the primary site) inflammatory carcinoma of the breast. The treatment was administered in three steps beginning with chemotherapy with doxorubicin, 5-fluorouracil, and cyclophosphamide. Tamoxifen was given to all patients, and the ovaries of premenopausal women were destroyed with radiation. A total mastectomy was then performed, along with the removal of lymph nodes from the armpit. After surgery, chemotherapy was again initiated, along with radiotherapy of the chest wall and armpits. The overall survival rate after five years was 75 percent, and the disease-free five-year survival rate from these patients was 48 percent, which compares well with other treatment regimens. The factor which correlated most strongly with survival was the response of the tumor to the initial chemotherapy. Patients with tumors that responded to the first three cycles of chemotherapy had an 80 percent rate of disease-free survival after five years. Patients with a residual tumor that remained larger than 1 cm after the initial chemotherapy had a 30 percent rate of disease-free survival after five years. (Consumer Summary produced by Reliance Medical Information, Inc.)

The fms-related tyrosine kinase 3 (FLT3) receptor has been extensively studied over the past two decades with regard to oncogenic alterations that do not only serve as prognostic markers but also as therapeutic targets in acute myeloid leukemia (AML). Internal tandem duplications (ITDs) became of special interest in this setting as they are associated with unfavorable prognosis. Because of sequence-dependent protein conformational changes FLT3-ITD tends to autophosphorylate and displays a constitutive intracellular localization. Here, we analyzed the effect of tyrosine kinase inhibitors (TKIs) on the localization of the FLT3 receptor and its mutants. TKI treatment increased the surface expression through upregulation of FLT3 and glycosylation of FLT3-ITD and FLT3-D835Y mutants. In T cell-mediated cytotoxicity (TCMC) assays, using a bispecific FLT3 × CD3 antibody construct, the combination with TKI treatment increased TCMC in the FLT3-ITD-positive AML cell lines MOLM-13 and MV4-11, patient-derived xenograft cells and primary patient samples. Our findings provide the basis for rational combination of TKI and FLT3-directed immunotherapy with potential benefit for FLT3-ITD-positive AML patients.

Antibody-dependent cellular cytotoxicity (ADCC) of natural killer (NK) cells largely contributes to the success of monoclonal antibody (mAb) treatment in cancer. As no antibodies are clinically available for immunotherapy of myeloid leukemias (MLs), we aimed to develop an Fc-optimized CD133 mAb for induction of NK ADCC against MLs. When comparing different available CD133 mAbs, no difference was observed with regard to binding to primary chronic myeloid leukemia cells. However, clone 293C3 recognized acute myeloid leukemia (AML) cells in a substantially higher percentage of patient cases and was thus chosen to generate chimeric mAbs with either wild-type Fc part (293C3-WT) or a variant containing amino-acid exchanges (S239D/I332E) to enhance affinity to CD16 on NK cells (293C3-SDIE). In vitro, treatment with 293C3-SDIE significantly enhanced activation, degranulation and lysis of primary CD133-positive AML cells by allogeneic and autologous NK cells as compared with its wild-type counterpart. In line with the observed lower expression levels of CD133 on healthy cells compared with malignant hematopoietic cells, 293C3-SDIE caused no relevant toxicity towards committed hematopoietic progenitor cells. In a NOD.Cg-PrkdcscidIL2rgtmWjl/Sz xenotransplantation model, 293C3-SDIE facilitated elimination of patient AML cells by human NK cells. Thus, 293C3-SDIE constitutes an attractive immunotherapeutic compound, in particular for elimination of minimal residual disease in the context of allogeneic stem cell transplantation in AML.

ABSTRACTBackground Secure messages exchanged between patients and family medicine residents via an electronic health record (EHR) could be used to assess residents' clinical and communication skills, but the mechanism is not well understood.Objective To design and test a secure messaging competency assessment for family medicine residents in a patient-centered medical home (PCMH).Methods Using the existing literature and evidence-based guidelines, we designed an assessment tool to evaluate secure messaging competency for family medicine residents training in a PCMH. Core faculty performed 2-stage validity and reliability testing (n 2 and n 9, respectively). A series of randomly selected EHR secure messages (n 45) were assessed from a sample of 10 residents across all years of training.Results The secure message assessment tool provided data on a set of competencies and a framework for resident feedback. Assessment showed 10 (n 2) of residents at the novice level, 50 (n 10) as progressing, and 40 (n 8) as proficient. The most common deficiencies for residents' secure messages related to communication rather than clinical competencies (n 37 90 versus n 4 10). Interrater reliability testing ranged from 60 to 78 agreement and 20 to 44 disagreement. Disagreement centered on interpersonal communication factors. After 2 stages of testing, the assessment using residents' secure messages was incorporated into our existing evaluation process.Conclusions Assessing family medicine residents' secure messaging for patient encounters closed an evaluation gap in our family medicine program, and offered residents feedback on their clinical and communication skills in a PCMH.

As a kind of long fibre reinforced thermoplastic, a new glass mat thermoplastic GMT-like material is introduced. It is designed to be suitable for various polymers and high glass fibre GF content, which might be a promising attempt to overcome the limit of conventional GMT material PP matrix and maximum 40 wt- GF. The concept is based on a multi-layered hybrid structure consisting of several thin GF sub-layers and polymer films having an inherently high viscosity. They are then needle-matted all together. The capability of higher GF content was derived from the porosity changes under pressure and the cross-sectional view after impregnation. It was finally confirmed by measurement of flexural properties up to 70 wt- of GF content in PP grade. Moreover, PA6 grade was investigated to show the other capability of multi-layered hybrid mat for various polymers.

The prospect of enhancing the hardness of low alloy steel for the manufacture of fasteners is examined using ausforming, in which the austenite is deformed rapidly at a low temperature to increase its dislocation density before quenching in order to obtain the harder martensite. Surprisingly, small deformations accomplish large gains in hardness and the dislocation density of martensite, with diminishing returns at larger deformations. The main contribution to the hardness has been identified as the extra dislocations inherited by the martensite from the deformed austenite, rather than the refinement of microstructure by the ausforming process. Clear evidence is reported for the mechanical stabilisation of the austenite due to ausforming. Tempering heat treatments tend to diminish the advantages of ausforming.

The surface quality of steels containing solutes that have a strong affinity for oxygen can be markedly compromised during processing at elevated temperatures. Here, we examine a class of steels that are being developed for low density applications and hence, have relatively large concentrations of aluminium and manganese. These two elements compete for what little oxygen is available in the predominantly hydrogen–nitrogen mixture used to protect the steel during heat treatment. It is found that although the general sequence of oxidation does not seem to vary as the aluminium concentration is increased, the stoichiometry of the oxides changes. Manganese rich oxide is always the first to form for all the dew points examined, but is rapidly overtaken by aluminium oxide when the dew point is kept below -30°C. In the latter case, the eventual formation of an alumina film also halts the internal oxidation of aluminium. The results obtained using a variety of high resolution microscopy and analytical techniques have been analysed by calculating phase diagrams and by creating a finite difference model to reveal aspects of the internal oxidation problem.

Although gradual bone transport may permit the restoration of large-diameter bones, complications are common owing to the long duration of external fixation. In order to reduce such complications, a new technique of bone transport involving the use of an external fixator and a locking plate was devised for segmental tibial bone defects.A total of ten patients (nine men, one woman) with a mean age at operation of 40.4 years (16 to 64) underwent distraction osteogenesis with a locking plate to treat previously infected post-traumatic segmental tibial defects. The locking plate was fixed percutaneously to bridge proximal and distal segments, and was followed by external fixation. After docking, percutaneous screws were fixed at the transported segment through plate holes. At the same time, bone grafting was performed at the docking site with the external fixator removed.The mean defect size was 5.9 cm (3.8 to 9.3) and mean external fixation index was 13.4 days/cm (11.8 to 19.5). In all cases, primary union of the docking site and distraction callus was achieved, with an excellent bony result. There was no recurrence of deep infection or osteomyelitis, and with the exception of one patient with a pre-existing peroneal nerve injury, all achieved an excellent or good functional result.With short external fixation times and low complication rates, bone transport with a locking plate could be recommended for patients with segmental tibial defects.Cite this article: Bone Joint J2013;95-B:1667–72.

Chronic arterial occlusion leads to growth of collaterals - a process termed arteriogenesis, in which macrophages play a prominent role in remodelling and growth. However, a detailed analysis which of distinct macrophage subpopulations involved in arteriogenesis has never been performed. In the present study the temporal and spatial distribution of macrophage subtypes during arteriogenesis in a rat model with chronically elevated fluid shear stress (FSS) is investigated. Local macrophage subpopulations were histologically immuno-phenotyped using CD68 (a ubiquitous macrophage marker) and CD163, a specific M2 macrophage marker. Without occlusion few M2-macrophages reside in the perivascular space. Early after occlusion (12h) the number of M2 macrophages increases strongly and M1 macrophages begin emerging into the collateral. After 3 days they appear in the perivascular space. Both macrophage subtypes increase until 28d after treatment, whereas M2 macrophages dominate at the site of collateral growth. The local distribution of the subpopulations changes during the arteriogenic process. Whereas M1 macrophages are detected directly adjacent to the media, M2 macrophages are present in the most outer perivascular region of the growing collateral vessel. Systemic alterations of blood leucocytes in mice after femoral artery ligature (FAL) were investigated by FACS analysis of serial blood samples. During collateral remodelling histological changes were not reflected in circulating monocytes in the peripheral blood. The activation state of macrophages in mice with FAL was modulated by injections of either dexamethasone or the interleukins IL10 or IL3/IL14. The arteriogenic response was assessed by hind limb perfusion with laser Doppler measurements after 3, 7 and 14d. Suppressing inflammatory monocyte subtypes (M1) with dexamethasone led to impaired perfusion recovery after FAL in mice, whereas IL10 or IL4/IL13 application significantly increased perfusion recovery. This investigation demonstrates that a forced shift towards M2 macrophages improves the arteriogenic response. The distinct early increase and spatial distribution of M2 macrophages support the idea that this subtype plays a predominant role during collateral remodelling.

We examine here the spot welding characteristics of transformation induced plasticity assisted steels, which contain δ-ferrite as a consequence of their aluminium concentrations of 3·5 or 5·6 wt-% and which also have high carbon contents of 0·3 or 0·4 wt-% when compared with conventional automotive steels. The resistance spot welds are tested in both shear and cross-tensile tests in order to determine the so called ductility ratio, which is a parameter associated with the fitness of such welds for automotive applications. With an increase in the δ-ferrite fraction from 0·19 to 0·5, the hardness variation across the weld and heat affected zone is decreased approximately from 400 to 150 HV. It seems that the presence of stable δ-ferrite is helpful in reducing hardness variations and in achieving a significant ductility ratio of 0·39.

Retrocyclins are humanized versions of the {theta}-defensin peptides expressed by the leukocytes of several nonhuman primates. Previous studies, performed in serum-free media, determined that retrocyclins 1 (RC1) and RC2 could prevent successful germination of Bacillus anthracis spores, kill vegetative B. anthracis cells, and inactivate anthrax lethal factor. We now report that retrocyclins are extensively bound by components of native mouse, human, and fetal calf sera, that heat-inactivated sera show greatly enhanced retrocyclin binding, and that native and (especially) heat-inactivated sera greatly reduce the direct activities of retrocyclins against spores and vegetative cells of B. anthracis. Nevertheless, we also found that retrocyclins protected mice challenged in vivo by subcutaneous, intraperitoneal, or intranasal instillation of B. anthracis spores. Retrocyclin 1 bound extensively to B. anthracis spores and enhanced their phagocytosis and killing by murine RAW264.7 cells. Based on the assumption that spore-bound RC1 enters phagosomes by "piggyback phagocytosis," model calculations showed that the intraphagosomal concentration of RC1 would greatly exceed its extracellular concentration. Murine alveolar macrophages took up fluorescently labeled retrocyclin, suggesting that macrophages may also acquire extracellular RC1 directly. Overall, these data demonstrate that retrocyclins are effective in vivo against experimental murine anthrax infections and suggest that enhanced macrophage function contributes to this property.

A reversible solid oxide fuel cell (RSOFC) provides the dual function of performing energy storage and power generation, all in one unit. When functioning as an energy storage device, the RSOFC acts like an electrolyzer in water electrolysis mode; whereby the electric energy is stored as (electrolyzed) hydrogen and oxygen gases. While hydrogen is useful as a transportation fuel and in other industrial applications, the RSOFC also acts as a fuel cell in power generation mode to produce electricity when needed. The RSOFC would be a competitive technology in the upcoming hydrogen economy on the basis of its low cost, simple structure, and high efficiency. This paper reports on the design and manufacturing of its membrane electrode assembly using commercially available materials. Also reported are the resulting performance, both in electrolysis and fuel cell modes, as a function of its operating parameters such as temperature and current density. We found that the RSOFC performance improved with increasing temperature and its fuel cell mode had a better performance than its electrolysis mode due to a limited humidity inlet causing concentration polarization.

Abstract: Compression ignition of homogeneous charges in internal combustion (IC) engines is expected to offer high efficiency of DI diesel engines without high levels of NOx and particulate emissions. This study is intended to find ways of extending the rich limit of HCCI operation, one of the problems yet to be overcome. Exhaust emissions characteristics are also explored through analyses of the combustion products. DME fuel, either mixed with air before induction or directly injected into the combustion chamber of a rapid compression and expansion machine, is compressed to ignite under various conditions of compression ratio, equivalence ratio, and injection timing. The characteristics of the resulting combustion and exhaust emissions are discussed in terms of the rate of heat release computed from the measured pressure, and the concentrations of THC, CO, and NOx are measured by FT-IR and CLD. The experimental data to date show that operation without knock is possible with mixtures of higher equivalence ratio when DME is directly injected rather than when it is inducted in the form of a perfectly homogeneous fuel-air mixture. Although fuel injected early in the compression stroke promotes homogeneity of the DME-air mixture in the cylinder, it causes the mixture to ignite too early to secure good thermal efficiency and knock-free operation at high loads. Low temperature reactions occur at about 660K regardless of the fueling methods, fuel injection timing and equivalence ratio. The main components of hydrocarbon emissions turned out to be unburned fuel (DME), formaldehyde and methane.

Abstract: This paper proposes a steering control method based on optimal control theory to improve the maneuverability of a six-wheeled vehicle during cornering. The six-wheeled vehicle is believed to have better performance than a four-wheeled vehicle in terms of its capability for crossing obstacles, off-road maneuvering and fail-safe handling when one or two of the tires are punctured. Although many methods to improve the four-wheeled vehicle’s lateral stability have been studied and developed, there have only been a few studies on the six-wheeled vehicle’s lateral stability. Some studies of the six-wheeled vehicle have been reported recently, but they are related to the desired yaw rate of a four-wheeled vehicle to control the six-wheeled vehicle’s maneuvering during corning. In this paper, the sideslip angle and yaw rate are controlled to improve the maneuverability during cornering by independent control of the steering angles of the six wheels. The desired yaw rate that is suitable for a six-wheeled vehicle is proposed as a control target. In addition, a scaled-down vehicle with six drive motors and six steering motors that can be controlled independently is designed. The performance of the proposed control methods is verified using a full model vehicle simulation and scaled-down vehicle experiment.

In this study, joining characteristics of dissimilar Ti and Cu metals have been investigated, when using both an Ag-based eutectic alloy as a filler and an Ag layer present on Ti base metal as a diffusion barrier. The observed microstructures were classified into three characteristic types, depending on the presence of a Ag layer at the Ti interface, e.g. first, the sample retaining thick continuous intermetallic layers, e.g. Ti2Cu, TiCu, Ti3Cu4, Ti2Cu3, and TiCu4 by a significant dissolution of the Ti atoms into the molten filler, in the absence of a Ag coating layer onto the Ti base metal, second, the sample with relatively thin Ti-Cu intermetallic layers by the reduced reaction of Ti with Cu due to a prominent decrease in the Ti dissolution, owing to the role of the Ag coating layer as a diffusion barrier, and finally, the sample without any brittle Ti-Cu intermetallics in the joint by a complete suppression of both the dissolution of the Ti atoms and its reaction with the Cu elements in the molten filler due to the presence of a Ag layer.

The microstructure and mechanical properties of Ti joints brazed with a Zr41.2Ti13.8Ni10.0Cu12.5Be22.5 (at.%) amorphous filler were investigated. With a Zr-based amorphous filler, in this study, Ti joints with a homogeneous composition could be obtained by heating to well below the α-β transformation temperature for a short time, so that the undesirable effects of the high temperature heating are considerably diminished. The joints brazed at 790 °C for 10 min consisted of the coarse acicular structure rather than the fine Widmanstätten structure which generally deteriorates the ductility of the joints. The joints with the homogenous coarse acicular structure, i.e. without a residual liquid region, show almost the same mechanical properties as those required for base metals without heating. Although the residual liquid region in the joints deteriorates the ductility of the joints, this region could be successfully removed by a diminution in the quantity of the filler.

Microfracture mechanisms of Zr-based bulk metallic glass (BMG) alloy containing ductile crystalline particles were investigated by directly observing microfracture processes using an in situ loading stage. Strength of the BMG alloy containing crystalline particles was lower than that of the monolithic BMG alloy, while ductility was higher. According to the direct microfracture observation, crystalline particles initiated shear bands, acted as blocking sites of shear band or crack propagation, and provided the stable crack growth which could be confirmed by the R-curve analysis, although they negatively affected apparent fracture toughness. This increase in fracture resistance with increasing crack length improved overall fracture properties of the alloy containing crystalline particles, and could be explained by mechanisms of blocking of crack or shear band propagation, formation of multiple shear bands, crack blunting, and shear band branching.

Development of wrought Mg alloys, particularly in sheet form, is essential to support the growing interest for lightweight components in the automotive industry. However, development of Mg alloy sheets has been quite slow due to the complexity of sheet production originated from limited deformability of Mg. In this respect, twin-roll strip casting, a one-step processing of flat rolled products, can be an alternative for the production of Mg alloy sheets. In this study, AZ31 and experimental ZM series alloys are twin-roll strip cast into 2 mm thick sheets. The microstructure of the as-cast AZ31 alloy sheet consists of columnar zones near the roll side and equiaxed zones in the mid-thickness region. On the other hand, as-cast ZM series alloy sheets show equiaxed dendritic structure through the thickness of sheet. These alloys were subjected to various thermo-mechanical treatments and their tensile properties were evaluated. Twin-roll strip cast AZ31 alloy in H24 condition has equivalent yield and tensile strengths with similar ductility compared to commercial ingot cast AZ31-H24 alloy, indicating that twin-roll strip casting is a viable process for the fabrication of Mg alloy sheets. The experimental ZM series alloys have a large volume fraction of fine dispersoid particles in the microstructure, resulting from the beneficial effect of twin-roll strip casting on microstructural refinement. It has been shown that the experimental ZM series alloys have superior tensile properties compared to commercial ingot cast AZ31-H24 alloy, suggesting the possibility of the development of new wrought Mg alloy sheets by twin-roll strip casting.

Weld modeling technology and control and mitigation techniques of residual stress and distortion have made a significant progress in the past decade. Q-Weld as the latest development in weld modeling technique can provide a solution in an extremely short time compared to a traditional thermo-elastic-plastic analysis. Three distortion control techniques, transient thermal tensioning, low stress non-distortion and in-process rolling, are discussed in this paper.

Highly dense Y2O3 ceramics have been fabricated by a magnetic pulsed compaction (MPC) which is capable of reaching a sufficiently high pressure (~1GPa) in a very short duration (a few microseconds), and a subsequent pressureless sintering at 1600℃. The Y2O3 green bodies with a relative density of about 68% were achieved by the application of the MPC process due to the effect of an enhanced rearrangement and a high speed movement of the particles, without the help of ceramic binder. Those compacts showed densities greater than 95%, which is very close to the theoretical density, after the subsequent pressureless sintering process at 1600 oC. The shrinkage rates of the diameter for the samples compacted by the MPC process were markedly reduced, when compared to those for the ones by the conventional compaction (CC) process.

Structurally diverse amino acids were prepared as versatile synthons for combinatorial chemistry. Using an optimized solid-phase synthesis by Strecker-three-component-reaction (S-3CR), two different polymer linker constructs carrying piperazine were investigated. (a) Acrylate derived base-labile linker yielded α-aminonitriles with N-alkylated piperazines via Hofmann elimination after quarternisation with an alkyl halide. The crude product purities were in the range of 54–87%. (b) A urethane type linker yielded α-aminonitriles with the free piperazine nitrogen when cleaved with acid and the product purities were 72–93%. The α-aminonitriles were easily converted to novel Nɛ– Fmoc-protected α-amino acids with α-(1-piperazinyl) and α-phenyl substituents.Structurally diverse amino acids were prepared as versatile synthons for combinatorial chemistry. Using an optimized solid-phase synthesis by Strecker-three-component-reaction (S-3CR), two different polymer linker constructs carrying piperazine were investigated. (a) Acrylate derived base-labile linker yielded α-aminonitriles with N-alkylated piperazines via Hofmann elimination after quarternisation with an alkyl halide. The crude product purities were in the range of 54–87%. (b) A urethane type linker yielded α-aminonitriles with the free piperazine nitrogen when cleaved with acid and the product purities were 72–93%. The α-aminonitriles were easily converted to novel Nɛ– Fmoc-protected α-amino acids with α-(1-piperazinyl) and α-phenyl substituents.

Solidification behavior of two Fe-base amorphous alloys during twin-roll strip casting has been investigated in the present study. Continuous cooling transformation (CCT) diagrams of both alloys were calculated using the heterogeneous nucleation theory coupled with thermal data obtained during cooling. Cooling sequence during twin-roll strip casting was also simulated. These were used for the determination of the optimum twin-roll strip casting conditions at which desirable solidification behavior could be achieved. It shows that twin-roll strip casting can continuously fabricate sheet product of Fe-base bulk amorphous alloys, despite their higher liquidus temperatures and larger differences between liquidus and glass transition temperatures (Tg) than those of other easier glass-forming bulk amorphous alloys.

To assess the attitudes of Korean physicians toward hormone therapy (HT) after publication of the Women's Health Initiative (WHI) study.

Neutral detergent fiber (NDF) is the most effective and measurable predictor of animal intake. About 70% of the variation in animal production is attributed to differences in intake potential of livestock feed. Sixteen molecular markers associated with NDF in four divergently selected smooth bromegrass (Bromus inermisL.) populations were selected from a previous study for further examination for possible use in a marker‐assisted selection (MAS) breeding program. The objectives of this experiment were to confirm the association of previously identified markers to NDF concentration in smooth bromegrass populations and to develop a marker‐based selection index. Marker and NDF data were analyzed and marker indices were constructed using data from the current and previous studies. Index scores were used to rank genotypes and create selection differentials on the basis of phenotypic data. Marker frequencies calculated on a subpopulation basis between the previous and current studies were highly unrepeatable. Nevertheless, of the 14 groups of marker indices, seven of which accounted for pedigree structure, one marker index appears to provide the greatest potential for use in MAS to reduce NDF across all four populations of smooth bromegrass. Where pedigree structure is known, selections made using this index would lead to the largest expected response per year and eliminate the need to collect phenotypic data for as long as linkage relationships remain intact. Where pedigree structure is unknown, a general marker index may be used, or phenotypic data can be utilized along with a marker index. However, inclusion of phenotypic data would necessitate a cost–benefit analysis.

The out-of-plane plane coherence length ?cof YBa2Cu3O7??superconductor has been evaluated by analysing the thermally activated magnetic vortex flux creep across superconducting CuO2layers. Current flow along CuO2layers has been ensured by patterning (103)/(013) oriented films into several macro-bridges positioned at different angles with respect to the crystalline planes. The bridge in which vortex creep occurs across the intrinsic potential of CuO2layers has been selected on the basis of the superconducting transition and current-voltage characteristics. Current-voltage characteristics of the selected bridge were analysed in the framework of the theoretical model of Barone et al(1990 J. Supercond.3155), which accounts for a vortex creep in a periodic potential. The estimated out-of-plane coherence length ?cranges between 0.11 and 0.30 nm for films with different oxygen and structural defect contents, consistently with values evaluated with different techniques and reported in the literature. The ?cvalue changes in different ways with changing critical temperature Tc, depending on the dominating type of oxygen vacancies and defects.

Resist detachment from the substrate during mold−substrate separation is one of the key challenges for nanoimprint lithography as the pitch of features decreases. We analyzed the problem by considering the surface and interfacial free energies of the initial state and the possible final states of the mold−polymer−substrate system and designed the chemistry of the system to provide the desired final state. We dramatically improved the resist adhesion to the substrate by assembling a monolayer of surface linker molecules on the substrate surface. A 37 nanowire pattern at 30 nm half-pitch was imprinted onto the surface-modified substrate.

Synthetic lipopeptides carrying the head group of bacterial lipoproteins are specific ligands of Toll-like receptors (TLR). The three fatty acids containing lipopeptides with the tripalmitoyl-S-glyceryl-cysteinyl N-terminus (Pam3Cys) are agonists of TLR2. The structurally related lipopeptides with a head group lacking the fatty acyl residue at the amino-terminus (Pam2Cys) stimulate TLR2 and 6. To investigate the influence of the peptide chain of lipohexapeptides with a free N-terminus with regard to their ability to enhance B-cell proliferation, a randomized S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-pentapeptide amide collection Pam2CysXXXXX and 5 × 19 subcollections (Pam2CysOXXXX, Pam2CysXOXXX, Pam2CysXXOXX, Pam2CysXXXOX, Pam2CysXXXXO, O: all protein amino acids except Cys) were prepared by parallel solid-phase synthesis. The collection represents synthetic lipopeptide analogues of the numerous bacterial lipoproteins and of mycoplasma lipoprotein. Each of the 95 subcollections is characterized by one defined and four degenerated amino acid positions thus comprising 194 individual lipopeptides with free N-terminal amino groups. High-performance liquid chromatography electrospray mass spectrometry (HPLC–ESI-MS) was applied for the analytical characterization of the lipohexapeptide amide subcollections and for the individual lipohexapeptide amides. The subcollections were tested for polyclonal activation of murine spleen cells, deconvolution led to highly active single S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-pentapeptide amides.

Resist adhesion to the mold is one of the challenges for nanoimprint lithography. The main approach to overcoming it is to apply a self-assembled monolayer of an organosilane release agent to the mold surface, either in the solution phase or vapor phase. We compared the atomic force microscopy, ellipsometry, reflection−absorption infrared spectroscopy, and contact angle results collected from substrates treated by two different application processes and found that the vapor-phase process was superior. The vapor-treated substrates had fewer aggregates of the silane molecules on the surface, because the lower density of the agent in the vapor phase was not conducive to aggregation formation, and received a superior coating of the releasing agent, because the vapor was more effective than the solution in penetrating into the nanoscale gaps of the mold. A pattern transfer of 20 parallel nanowires with a line width of 40 nm at 100 nm pitch-size was performed faithfully with the vapor-treated mold without any resist adhesion.

Kentucky bluegrass (Poa pratensisL.) is an important cool‐season grass species in the turfgrass and forage industries. Understanding the genetics of Kentucky bluegrass is useful in developing improved cultivars and hybrids. However, studying the genetics of Kentucky bluegrass can often be difficult because of the high variation in ploidy level that results from its facultative apomictic reproductive nature. Flow cytometry provides an easy and accurate method for assessing this variation by quantifying DNA content. The purpose of our study was to determine the level of variation in ploidy in Kentucky bluegrass by analyzing its DNA content using flow cytometry. In addition, DNA content was compared with genetic similarity derived from DNA marker data, and was also correlated with chromosome number. Twenty‐two cultivars of Kentucky bluegrass were selected for the study by considering the range of variability in morphological traits and genetic distance derived from DNA marker data. We found that the DNA content of Kentucky bluegrass genotypes from the 22 cultivars ranged from 5.39 to 17.69 pg of DNA/2C and that a majority of the genotypes had a DNA content value in the range of 7 to 13 pg. A significant correlation between DNA content and chromosome number was detected. Euploid chromosome numbers (x= 7) with a range from the pentaploid (2n= 5x= 35) to the quindecaploid (2n =15x= 105) were found along with aneuploid numbers. The results of this research could aid both breeders and researchers in studying the genetics of the species and in improving Kentucky bluegrass cultivars via intra‐ and interspecific hybridizations.

Kentucky bluegrass (Poa pratensisL.) is a widely used, facultatively apomictic, cool season turf and forage grass, with many known cultivars. Previously these have been classified on the basis of morphological traits in field tests. However, these determinations are lengthy, sensitive to environmental variations, and there are few traits that can be tested. Molecular markers provide an alternative way to classify these cultivars. Important advantages of molecular markers include lack of sensitivity to changes in environmental conditions, as well as a nearly unlimited potential number of markers and speed of the marker assays as compared with field tests. They can also provide additional information such as the amount of genetic divergence between Kentucky bluegrass cultivars and other genotypes, the amount of agreement between morphological and marker‐based classification, and the amount of genetic variability between seedling replicates of genotypes. Random amplified polymorphic DNA (RAPD) marker data was collected from three replicates each of 123 Kentucky bluegrass cultivars, plant introductions (PIs), experimental breeding lines, and interspecific hybrids between Kentucky and Texas bluegrass (Poa arachniferaTorr.). From these data multidimensional scaling (MDS) plots were created, and ANOVA tests of significant differences between germplasm sources were performed. The PIs were the most genetically divergent from the cultivars, while the interspecific hybrids were not as distinct. Members of two morphological trait‐based types were found to be genetically similar, and there was a wide range of genetic variability among germplasm sources. The genetic divergence of the PIs, combined with their potentially high turf utility reported in earlier studies, indicates their potential as a genetic resource. All but two of the morphological trait‐based types contained genetically diverse individuals, so that cultivar blends of all but these two types would be morphologically similar yet genetically diverse. The rather high within‐cultivar genetic variability could be due to a relatively high proportion of potentially sexually produced off‐types. Thus, this study provides further evidence for the utility of RAPD markers for turfgrass genetics, as well as important genetic information for turf breeders and managers.

Optimized coupling protocols are presented for the efficient and automated generation of carboxyfluorescein-labeled peptides. Side products, generated when applying earlier protocols for the in situ activation of carboxyfluorescein, were eliminated by a simple procedure, yielding highly pure fluorescent peptides and minimizing postsynthesis workup. For the cost-efficient labeling of large compound collections, coupling protocols were developed reducing the amount of coupling reagent and fluorophore. To enable further chemical derivatization of carboxyfluorescein-labeled peptides in solid-phase synthesis, the on-resin introduction of the trityl group was devised as a protecting group strategy for carboxyfluorescein. This protecting group strategy was exploited for the synthesis of peptides labeled with two different fluorescent dyes, essential tools for bioanalytical applications based on fluorescence resonance energy transfer (FRET). Tritylation and optimized labeling conditions led to the development of a fluorescein-preloaded resin for the automated synthesis of fluorescein-labeled compound collections with uniform labeling yields.

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Oscillapeptin J (1), a new and highly potent crustacean grazer toxin, was isolated from the axenic cyanobacterium Planktothrix rubescens, which frequently forms blooms in freshwater lakes. Chemical and spectroscopic analyses, including high resolving MS and two-dimensional NMR, were used to elucidate the compound's structure as a depsiheptapeptide of the oscillapeptin type. Strict application of a bioassay-guided isolation procedure proved this compound to be one of the major causative agents (besides [d-Asp³,(E)-Dhb⁷]microcystin-RR) of the acute grazer toxicity of P. rubescens from Lake Zürich. The LC50 value of oscillapeptin J as determined for the freshwater crustacean Thamnocephalus platyurus was 15.6 μM.

Enhanced cellular immune response to bovine beta-casein has been reported in patients with type 1 diabetes. In this study we aimed to establish beta-casein-specific T cell lines from newly diagnosed type 1 diabetic patients and to characterise these cell lines in terms of phenotype and epitope specificity. Furthermore, since sequence homologies exist between beta-casein and putative beta-cell autoantigens, reactivity to the latter was also investigated. T cell lines were generated from the peripheral blood of nine recent onset type 1 diabetic patients with different HLA-DQ and -DR genotypes, after stimulation with antigen pulsed autologous irradiated antigen presenting cells (APCs) and recombinant human interleukin-2 (rhIL-2). T cell line reactivity was evaluated in response to bovine beta-casein, to 18 overlapping peptides encompassing the whole sequence of beta-casein and to beta-cell antigens, including the human insulinoma cell line, CM, and a peptide from the beta-cell glucose transporter, GLUT-2. T cell lines specific to beta-casein could not be isolated from HLA-matched and -unmatched control subjects. beta-Casein T cell lines reacted to different sequences of the protein, however a higher frequency of T cell reactivity was observed towards the C-terminal portion (peptides B05-14, and B05-17 in 5/9 and 4/9 T cell lines respectively). Furthermore, we found that 1 out of 9 beta-casein-specific T cell lines reacted also to the homologous peptide from GLUT-2, and that 3 out of 4 of tested cell lines reacted also to extracts of the human insulinoma cell line, CM. We conclude that T cell lines specific to bovine beta-casein can be isolated from the peripheral blood of patients with type 1 diabetes; these cell lines react with multiple and different sequences of the protein particularly towards the C-terminal portion. In addition, reactivity of beta-casein T cell lines to human insulinoma extracts and GLUT-2 peptide was detected, suggesting that the potential cross-reactivity with beta-cell antigens deserves further investigation.

Bacterial brown spot (BBS), caused by Pseudomonas syringaepv. syringaevan Hall (Pss), is an important bacterial disease of common bean (Phaseolus vulgarisL.). The objective of this study was to identify random amplified polymorphic DNA (RAPD) molecular markers linked to quantitative trait loci (QTLs) for BBS resistance. Resistance was assessed by three methods: (i) stem inoculations of plants grown in a greenhouse evaluated by a 1‐to‐5 rating scale for stem symptoms, (ii) percentage of BBS infected leaves per plot in noninoculated field trials, and (iii) Psspopulation sizes, on noninoculated field grown plants determined by a leaflet freezing assay (LFA). F8:9recombinant inbred lines derived from the Mesoamerican cross of Belneb RR‐1 (susceptible to BBS) × A 55 (resistant to BBS) were grown in replicated experiments in two years (1996, 1998) in Wisconsin. In addition, two separate experiments were performed in the greenhouse in a randomized complete block design with two replicates for seedling stem inoculation with Pssstrain Bs191. One genomic region on linkage group (LG) 2, from a previously published genetic linkage map, was significantly associated with QTLs for BBS resistance measured by three assays over two years. Phenotypic reactions were significantly correlated with the measurement of freezing temperatures as determined by LFA under a favorable environment for the growth of epiphytic bacterial populations. Marker assisted selection for resistance to BBS using molecular markers found during this study may improve selection efficiency for resistance because of the low heritability of the reaction to BBS, and the independent QTLs for resistance to different bacterial diseases. Furthermore, disease screening solely dependent upon natural field inoculations is not reliable because of genotype × environment interactions. The leaflet freezing assay method could be utilized to screen progenies or breeding germplasms, even when no distinct phenotypic disease symptoms are present on the plants.

Acyclic diastereoselection is achieved for the formation of thioaminyl acetals. The highly intramolecular stereocontrolled SN2 displacement of the thioaminyls allows for the formation of cyclic nucleoside derivatives. This versatile approach may provide easy access to a large variety of N-glycosides.

Fusarium oxysporumSchlectend. Fr. f. sp. phaseoliJ.B. Kendrick and W.C. Snyder (FOP) is a vascular pathogen that causes Fusarium wilt in common bean (Phaseolus vulgarisL.). This disease is an increasing problem in the western U.S., and exploitation of genetic resistance is considered the most feasible control method. The objective of this study was to detect quantitative trait loci (QTL) for Fusarium wilt resistance in a population derived from an interracial cross between FOP‐susceptible Belneb RR‐1 (race Durango) × FOP‐resistant A55 (race Mesoamerica). Seventy‐six F6‐derived recombinant inbred lines (RILs) were screened for disease severity in greenhouse inoculations and rated on a scale of 1 (resistant) to 9 (susceptible). The phenotypic data were compared to existing random amplified polymorphic DNA (RAPD) marker data using single‐factor analysis of variance. Marker U20.750 on linkage group (LG) 10 accounted for 63.5% of the phenotypic variance for this trait. Lines exhibiting the A55 banding pattern at this locus had disease severity scores that averaged 3.6 points lower than lines with the Belneb RR‐1 pattern. Two additional markers, AD4.450 on LG 3 and K10.700 on LG 11, were significant (P< 0.01) in single‐factor analysis of variance, but only marker U20.750 on LG 10 remained significant when composite interval mapping (CIM) was conducted. The tight linkage between the putative QTL and U20.750, as indicated by CIM, makes this marker a promising candidate for conversion to a sequence‐characterized amplified region (SCAR) for use in marker‐assisted selection in Fusarium wilt resistant common bean cultivar development.

The diastereoselectivity of radical processes involving 1,3-diols is increased significantly with a simple and efficient strategy using the exocyclic effect. Boronate derivatives are successfully formed in situ by treatment of an equimolar amount of Et3B in the presence of oxygen. This step is followed by the mediation of a carbon-centered radical α to the cyclic boronate to give the anti reduced product with high stereocontrol. The sequence is also extended to β-amino alcohols.

In this paper, we focus on the synthesis and structure of the new bis(1,3,4-oxadiazole) system 2,5-bis[2-(4-tert-butylphenyl)-1,3,4-oxadiazol-5-yl]pyridine (PDPyDP). We have fabricated light-emitting diodes (LEDs) using poly[2-methoxy-5-(2-ethylhexoxy)-1,4-phenylene vinylene] (MEH−PPV) as the emissive material, with and without a thermally evaporated electron-injection/hole-blocking layer of either PDPyDP or its vinylene analogue (E)-1,2-bis[2-(4-tert-butylphenyl)-1,3,4-oxadiazol-5-yl]ethene (PDVDP) or its phenylene analogue 1,4-bis[2-(4-tert-butylphenyl)-1,3,4-oxadiazol-5-yl]benzene (PDPDP). PDPDP is the para isomer of OXD-7, which is a widely used molecular electron-transporting material. Electroluminescence spectra indicate that light is emitted only from the MEH−PPV layer. Using aluminum as the cathode, the bilayer LED with PDPyDP is considerably more efficient than the corresponding single-layer device or devices with PDVDP or PDPDP as the electron-injection layer.