The Raf/MEK/MAPK signaling module elicits a strong negative impact on skeletal myogenesis that is reflected by a complete
loss of muscle gene transcription and differentiation in multinucleated ...myocytes. Recent evidence indicates that Raf signaling
also may contribute to myoblast cell cycle exit and cytoprotection. To further define the mechanisms by which Raf participates
in cellular responses, a stable line of myoblasts expressing an estrogen receptor-Raf chimeric protein was created. The cells
(23A2RafER DD ) demonstrate a strict concentration-dependent increase in chimeric Raf protein synthesis and downstream phosphoMAPK activation.
Initiation of low-level Raf activity in these cells augments contractile protein expression and myocyte fusion. By contrast,
induction of high level Raf activity in 23A2RafER DD myoblasts inhibits the formation of myocytes and muscle reporter gene expression. Interestingly, treatment of myoblasts with
conditioned medium isolated from Raf-repressive cells inhibits all of the aspects of myogenesis. Closer examination indicates
that the transforming growth factor-β 1 (TGF-β 1 ) gene is up-regulated in Raf-repressive myoblasts. The cells also direct elevated levels of Smad transcriptional activity,
suggesting the existence of a TGF-β 1 autocrine loop. However, extinguishing the biological activity of TGF-β 1 does not restore the myogenic program. Our results provide evidence for the involvement of Raf signal transmission during
myocyte formation as well as during inhibition of myogenesis.
Two novel analogues of lysine have been prepared in high enantiomeric and diastereomeric purity. These unnatural α-amino acids possess modified aminoalkyl side chains incorporating a pyrrolidine ...nucleus as a cyclic constraint.
Novel lysine analogues
2a and
2b, in which the aminoalkyl side chain incorporates a pyrrolidine nucleus as a cyclic constraint, have been prepared in high enantio- and diastereomeric purity.
Analyses of CuBr and CuN(CN)
2 used in the preparation of κ-(ET)
2CuN(CN)
2Br reveal both magnetic (1–42 ppm) and nonmagnetic (1–5%) contaminants. Markedly different resistivity profiles are obtained ...for κ-(ET)
2CuN(CN)
2Br samples prepared from various Cu(I) sources; some profiles show little or no resistive hump near 100 K. Rotating disk voltammetry studies indicate that the E
1/2 values for ET and the CuN(CN)
2Br anion are similar. Accordingly, considerable quantities of Cu(II) must be produced during the electrochemical synthesis of κ-(ET)
2CuN(CN)
2Br. Whether Cu(II) that is generated in this manner is incorporated into κ-(ET)
2CuN(CN)
2Br is under investigation.
OBJECTIVE: To compare the scholarly productivity index (SPI) among the levels of academic appointment, degree type, and percentage of academic appointment of athletic training faculty members. DESIGN ...AND SETTING: We used a 5 x 6 x 4 factorial design for this study. A survey instrument was used to determine the number of publications and the number of years in their current appointment. SUBJECTS: Subjects were faculty members in Commission on Accreditation of Allied Health Education Programs-accredited athletic training education programs. MEASUREMENTS: The SPI was calculated by dividing the total number of publications (peer-reviewed and non-peer-reviewed journal articles, peer-reviewed abstracts, books written or edited, book chapters, platform presentations, published book reviews, and external funding) by the number of years in the productivity period. RESULTS: The SPIs were different for the levels of academic rank. Full professors had a higher SPI than all other groups (Tukey honestly significant difference, P </=.05). Associate professors had higher SPIs than instructors or lecturers and clinical specialists, equivalent SPIs to assistant professors, and lower SPIs than full professors. Assistant professors had lower SPIs than full professors but were equivalent to all other groups. There were no differences among the levels of degree type or percentage of academic appointment. CONCLUSIONS: The scholarly productivity of athletic training educators was affected by their academic rank but not by the percentage of time they were assigned to academics or their academic degree type.
Abstract Objective: To assess the value of an open access echocardiography service. Design: Study of new open access service for general practitioners, who were invited to refer patients taking ...diuretics for suspected heart failure, untreated patients with symptoms of possible heart failure, and asymptomatic patients with risk factors for left ventricular systolic dysfunction. Setting: Regional cardiology centre. Subjects: 259 consecutive patients. Main outcome measures: Presence or absence of left ventricular systolic dysfunction and consequent changes in clinical management. Results: 119 treated patients, 99 untreated patients, and nine asymptomatic patients were referred over five months. 32 were considered to be inappropriately referred. Among the treated patients, 31 had impaired left ventricular systolic function and five had valvular disease; angiotensin converting enzyme inhibitors were recommended for 34 of these patients. In addition, 53 were thought not to need diuretics. Eight untreated patients had impaired systolic function and six valvular disease. Conclusions: The service was well used by general practitioners and led to advice to change management in more than two thirds of patients. Key messages Key messages Without accurate diagnosis many patients will be treated inappropriately Echocardiography allows rapid confirmation of the diagnosis Providing general practitioners with open access to echocardiography led to a change in treatment being recommended for 70% of patients taking diuretics for suspected heart failure The open access service was popular with general practitioners and did not lead to an unmanageable increase in workload
The non-axisymmetric magnetic field, naturally present in every tokamak, constraints the machine operational space. A set of dedicated ‘Error Field Correction Coils’ (EFCC) is proposed for JET, which ...will replace the unreliable existing ‘saddle coils’. The new coils are specified to compensate the main harmonic contribution to error field induced modes. The EFCC structural design comprises a cable coil wound in a metallic casing supported on the JET iron magnetic circuit. Existing power supplies will drive the coils. The EFCC are expected to be installed in 2001 JET shutdown.
The GRANIT system operates by applying an impulse of known force by means of an impact device that is attached to the tendon of the anchorage. The vibration response signals resulting from this ...impulse are complex in nature and require analysis to be undertaken in order to extract information from the vibrational response signatures that is relevant to the condition of the anchorage. In the system, the complicated relationship that exists between characteristics of an anchorage and its response to an impulse is identified and learned by a novel artificial intelligence network based on artificial intelligence techniques. The results presented in this paper demonstrate the potential of the GRANIT system to diagnose the integrity of ground anchorages at a site near Stone, England, by using a trained neural network capable of diagnosing the post-tension level of the anchorage. This neural network was used for the diagnosis of load in a second ground anchorage adjacent to the original anchorage used for the training of the neural network. Further tests were taken with a different anchor head configuration of the anchorage and a different relationship between the signature response of the anchorage to an applied impulse and its post-tension level was found. Problems encountered during the diagnosis of this second set of test signatures by the trained neural network are investigated with the use of a lumped parameter dynamic model. This model is able to identify the parameters in the anchorage system that affect this change in response signature. The results from the investigation lead to a new form of classification for the installed anchorages, based on their anchor head configuration. Laboratory strand anchorage tests were undertaken in order to compare with and validate the results obtained from the field tests and the lumped parameter dynamic model.
Human decidua contains resident decidual cells alongside a population of bone marrow-derived cells, among which macrophages and large granular lymphocytes are most abundant. We hypothesized that ...soluble effectors produced by bone marrow-derived cells may modulate the function of the decidual cells. To investigate this, a cell purification protocol was devised that involved digestion of first-trimester decidua with collagenase and hyaluronidase to produce a mixed stromal cell suspension from which the bone marrow-derived cells were removed using immunomagnetic beads coated with anti-CD45. The resulting stromal cells were maintained in culture in the presence of progesterone and were found to produce PRL. The effect of a panel of cytokines on PRL production was examined. Tumor necrosis factors-alpha and -beta had a dose-dependent inhibitory effect, and tumor necrosis factor receptors were identified on the cells. Interleukin 1 alpha and 1 beta, platelet-derived growth factor, and transforming growth factor-beta 1 were also found to inhibit PRL production, and platelet-derived growth factor and transforming growth factor-beta 1 stimulated cell proliferation. These findings suggest an interaction between the immune and endocrine systems in regulating the maternal environment of early pregnancy.
OBJECTIVE--To establish and compare the characteristics of older (greater than or equal to 70 years) and younger patients with chest pain selected to undergo coronary angiography and by analysis of ...their subsequent management to assess the value of coronary angiography for older patients with chest pain. DESIGN--Retrospective analysis of clinical case notes and coronary angiography reports. SETTING--Cardiology department with referral population of one million in an Edinburgh hospital. PATIENTS--134 consecutive patients with chest pain aged 70 years or over investigated by coronary angiography between 1978 and 1988; 134 randomly selected patients aged under 70 investigated over the same period. MAIN OUTCOME MEASURES--Clinical and angiographic features at time of angiography and management after angiography. RESULTS--Older patients represented a small, but increasing, proportion of those investigated. Older patients had more severe symptoms at the time of angiography, were taking more antianginal drugs, and had had their symptoms for longer than younger patients. At angiography more older patients had triple vessel coronary disease, left main stem stenosis, or left ventricular impairment. After angiography similar proportions of older and younger patients underwent coronary artery surgery, with more elderly patients requiring urgent operation; although operative mortality was higher for elderly patients, symptomatic benefit was similar to that in younger patients. CONCLUSIONS--Older patients with angina selected to undergo coronary angiography and subsequent coronary surgery have more severe symptoms and underlying cardiac disease. Earlier referral and investigation might yield a population with lower operative risk. Selection of patients for coronary angiography and coronary artery surgery should be based on the potential for benefit and should avoid "agism."
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