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Mass spectrometry of fragments produced by limited proteolytic digestion of pro-enkephalin was used to locate the disulfide bridges in synenkephalin (pro-enkephalin 1-73), a domain which contains sorting information for targeting the pro-neuropeptide to the granules of the regulated secretory pathway in neuroendocrine cells. Mass spectrometric analysis was optimized by using chemicals that gave low interference with the ionization and desorption processes, and computer software which simplified the identification of all possible disulfide-linked peptide fragments. Three disulfide bridges between Cys2-Cys24, Cys6-Cys28, and Cys9-Cys41 were identified. Protein conformational prediction of synenkephalin1-42 shows beta-turns which facilitate the formation of these disulfide bonds.

BackgroundReduced functional capacity and postexertion fatigue after physical activity are hallmark symptoms of chronic fatigue syndrome (CFS) and may even qualify for biomarker status. That these symptoms are often delayed may explain the equivocal results for clinical cardiopulmonary exercise testing in people with CFS. Test reproducibility in people who are healthy is well documented. Test reproducibility may not be achievable in people with CFS because of delayed symptoms.ObjectiveThe objective of this study was to determine the discriminative validity of objective measurements obtained during cardiopulmonary exercise testing to distinguish participants with CFS from participants who did not have a disability but were sedentary.DesignA prospective cohort study was conducted.MethodsGas exchange data, workloads, and related physiological parameters were compared in 51 participants with CFS and 10 control participants, all women, for 2 maximal exercise tests separated by 24 hours.ResultsMultivariate analysis showed no significant differences between control participants and participants with CFS for test 1. However, for test 2, participants with CFS achieved significantly lower values for oxygen consumption and workload at peak exercise and at the ventilatory or anaerobic threshold. Follow-up classification analysis differentiated between groups with an overall accuracy of 95.1%.LimitationsOnly individuals with CFS who were able to undergo exercise testing were included in this study. Individuals who were unable to meet the criteria for maximal effort during both tests, were unable to complete the 2-day protocol, or displayed overt cardiovascular abnormalities were excluded from the analysis.ConclusionsThe lack of any significant differences between groups for the first exercise test would appear to support a deconditioning hypothesis for CFS symptoms. However, the results from the second test indicated the presence of CFS-related postexertion fatigue. It might be concluded that a single exercise test is insufficient to reliably demonstrate functional impairment in people with CFS. A second test might be necessary to document the atypical recovery response and protracted fatigue possibly unique to CFS, which can severely limit productivity in the home and workplace.

Variation at the pleiomorphic adenoma gene 1 (PLAG1) locus has recently been implicated in the regulation of stature and weight in Bos taurus. Using a population of 942 outbred Holstein-Friesian dairy calves, we report confirmation of this effect, demonstrating strong association of early life body weight with PLAG1 genotype. Peripubertal body weight and growth rate were also significantly associated with PLAG1 genotype. Growth rate per kilogram of body weight, daily feed intake, gross feed efficiency and residual feed intake were not significantly associated with PLAG1 genotype. This study supports the status of PLAG1 as a key regulator of mammalian growth. Further, the data indicate the utility of PLAG1 polymorphisms for the selection of animals to achieve enhanced weight gain or conversely to aid the selection of animals with lower mature body weight and thus lower maintenance energy requirements.

For pt.I see ibid., vol.9, p.366-75 (1990). Presents approaches for the realization of fast electro-optical reconstruction systems for fan-beam projection data. Two of the proposed systems were implemented. Requiring only 30 ms for the reconstruction of one image, the systems are two orders of magnitude faster than the special-purpose hardware in commercial CT reconstruction systems. The speed of the reconstruction systems would allow real-time interactive CT imaging. >

To determine the validity and reliability of Short Form 36 Version 2 (SF36v2) in sub-groups of individuals with fatigue.Thirty subjects participated in this study, including n = 16 subjects who met case definition criteria for chronic fatigue syndrome (CFS) and n = 14 non-disabled sedentary matched control subjects. SF36v2 and Multidimensional Fatigue Inventory (MFI-20) were administered before two maximal cardiopulmonary exercise tests (CPETs) administered 24 h apart and an open-ended recovery questionnaire was administered 7 days after CPET challenge. The main outcome measures were self-reported time to recover to pre-challenge functional and symptom status, frequency of post-exertional symptoms and SF36v2 sub-scale scores.Individuals with CFS demonstrated significantly lower SF36v2 and MFI-20 sub-scale scores prior to CPET. Between-group differences remained significant post-CPET, however, there were no significant group by test interaction effects. Subjects with CFS reported significantly more total symptoms (p0.001), as well as reports of fatigue (p0.001), neuroendocrine (p0.001), immune (p0.01), pain (p0.01) and sleep disturbance (p0.01) symptoms than control subjects as a result of CPET. Many symptom counts demonstrated significant relationships with SF36v2 sub-scale scores (p0.05). SF36v2 and MFI-20 sub-scale scores demonstrated significant correlations (p0.05). Various SF36v2 sub-scale scores demonstrated significant predictive validity to identify subjects who recovered from CPET challenge within 1 day and 7 days (p0.05). Potential floor effects were observed for both questionnaires for individuals with CFS.Various sub-scales of SF36v2 demonstrated adequate reliability and validity for clinical and research applications. Adequacy of sensitivity to change of SF36v2 as a result of a fatiguing stressor should be the subject of additional study.

To determine the diagnostic accuracy for single symptoms and clusters of symptoms to distinguish between individuals with and without chronic fatigue syndrome (CFS). A cohort study was conducted in an exercise physiology laboratory in an academic setting. Thirty subjects participated in this study (n = 16 individuals with CFS; n = 14 non-disabled sedentary matched control subjects). An open-ended symptom questionnaire was administered 1 week following the second of two maximal cardiopulmonary exercise tests administered 24 h apart. Receiver operating characteristics (ROC) curve analysis was significant for failure to recover within 1 day (area under the curve = 0.864, 95% confidence interval [CI]: 0.706-1.00, p = 0.001) but not within 7 days. Clinimetric properties of failure to recover within 1 day to predict membership in the CFS cohort were sensitivity 0.80, specificity 0.93, positive predictive value 0.92, negative predictive value 0.81, positive likelihood ratio 11.4, and negative likelihood ratio 0.22. Fatigue demonstrated high sensitivity and modest specificity to distinguish between cohorts, while neuroendocrine dysfunction, immune dysfunction, pain, and sleep disturbance demonstrated high specificity and modest sensitivity. ROC analysis suggested cut-point of three associated symptoms (0.871, 95% CI: 0.717-1.00, p 0.001). A significant binary logistic regression model (p 0.001) revealed immune abnormalities, sleep disturbance and pain accurately classified 92% of individuals with CFS and 88% of control subjects. A cluster of associated symptoms distinguishes between individuals with and without CFS. Fewer associated symptoms may be necessary to establish a diagnosis of CFS than currently described.

We are reporting, for the first time, the echocardiographic identification of a bicuspid pulmonary valve associated with congenitally corrected transposition of the great arteries.

We report the first detection of chloronium, H$_2$Cl$^+$, in the interstellar medium, using the HIFI instrument aboard the \emph{Herschel} Space Observatory. The $2_{12}-1_{01}$ lines of ortho-H$_2^{35}$Cl$^+$ and ortho-H$_2^{37}$Cl$^+$ are detected in absorption towards NGC~6334I, and the $1_{11}-0_{00}$ transition of para-H$_2^{35}$Cl$^+$ is detected in absorption towards NGC~6334I and Sgr~B2(S). The H$_2$Cl$^+$ column densities are compared to those of the chemically-related species HCl. The derived HCl/H$_2$Cl$^+$ column density ratios, $\sim$1--10, are within the range predicted by models of diffuse and dense Photon Dominated Regions (PDRs). However, the observed H$_2$Cl$^+$ column densities, in excess of $10^{13}$~cm$^{-2}$, are significantly higher than the model predictions. Our observations demonstrate the outstanding spectroscopic capabilities of HIFI for detecting new interstellar molecules and providing key constraints for astrochemical models., Comment: Accepted for publication in A&A, HIFI Special Issue; 4 pages, 2 figures, 1 table

We describe a strategy for including ligand and protein polarization in docking that is based on the conversion of induced dipoles to induced charges. Induced charges have a distinct advantage in that they are readily implemented into a number of different computer programs, including many docking programs and hybrid QM/MM programs; induced charges are also more readily interpreted. In this study, the ligand was treated quantum mechanically to avoid parametrization issues and was polarized by the target protein, which was treated as a set of point charges. The induced dipole at a given target atom, due to polarization by the ligand and neighboring residues, was reformulated as induced charges at the given atom and its bonded neighbors, and these were allowed to repolarize the ligand in an iterative manner. The final set of polarized charges was evaluated in docking using AutoDock 4.0 on 12 protein-ligand systems against the default empirical Gasteiger charges, and against nonpolarized and partially polarized potential-derived charges. One advantage of AutoDock is that the best rmsd structure can be identified not only from the lowest energy pose but also from the largest cluster of poses. Inclusion of polarization does not always lead to the lowest energy pose having a lower rmsd, because docking is designed by necessity to be rapid rather than accurate. However, whenever an improvement in methodology, corresponding to a more thorough treatment of polarization, resulted in an increased cluster size, then there was also a corresponding decrease in the rmsd. The options for implementing polarization within a purely classical docking framework are discussed.2008112

It is proposed that all peptide hormones and releasing factors are biosynthesized in the form of precursor molecules which are biologically inactive. Enzymic activation may take place by hydrolytic cleavage to release a terminal COOH group or by transmidation to form a COOH-terminal amide. Studies with pituitary prohormones and hormones are providing data that support this hypothesis. Evidence has been obtained that the 91 residue beta-lipotropin (beta-LPH) is the prohormone of beta-melanotropin (beta-MSH). The specificity of the pituitary enzymes involved in release of the hormone was demonstrated by the isolation of five constituent fragments of LPH, which were obtained in homogeneous form from the pituitary gland of the pig. The enzymes have specificities similar to trypsin and carboxypeptidase B; carboxypeptidase A and aminopeptidase activities do not appear to be involved. Mild digestion of beta-LPH by trypsin in vitro has confirmed the susceptibility of the peptide bond on the carboxy side of the paired basic residues at positions 59 and 60, adjacent to the COOH-terminus of beta-MSH, and tryptic digestion of a model peptide demonstrated the same specificity. The paired basic residues at positions 39 and 40 adjacent to the NH2-terminus of beta-MSH were more resistant to tryptic attack, both in LPH and in a model peptide. In the gland it is apparent that LPH is cleaved on the carboxy side of the paired lysyl residues at positions 39 and 40, whereas in the synthetic peptide cleavage takes place in between these residues. The activating enzyme may differ from trypsin; alternatively, explanation may be found in the conformation of the prohormone. Prediction of secondary indicates that both pairs of basic residues lie adjacent to beta-bends on the surface of the molecule and occupy sites accessible to enzymic attack. It seems likely that alpha-MSH and corticotropin (ACTH) share a common pro hormone. The release of ACTH could involve cleavage of a -Gly-Ser- bond in the prohormone to expose the NH2-terminus of the hormone. With alpha-MSH, a concerted acetylation and cleavage may take place to form the N-acetylserine residue; the COOH-terminus may be released as an amide by direct transamidation of a -Val-Gly- bond in the prohormone. Release of either hormone would be accompanied by the release of contiguous fragments of the prohormone. We have isolated two novel polypeptides from pig pituitary in substantial quantity and have determined the primary structures. They may represent fragments of a prohormone to alpha-MSH or ACTH.

Issues concerning the certification of thermographers continue to command a great deal of interest within our profession and among the customers we serve. A recent literature search suggests the topic is as poorly understood as ever. In the United States the only viable means of establishing certification is through compliance, to one degree or another, with the standards and guidelines of the American Society for Nondestructive Testing (ASNT). These means, which, interestingly, also serve well the needs of ten additional NDT methods, are widely recognized throughout much of the rest of the world. Unfortunately for thermographers and their customers, ASNT-compliant certification for our NDT method has failed to gain significant "traction" over the years despite being used by a number of large companies and for many critical applications. The reasons are numerous and diverse. However, the gap has also not been filled by any other viable means of certification. One of the consequences of our failure to embrace uniform, meaningful certification is that our impact has been inconsistent and falls far short of the optimum possible. The framework for qualifying and certifying thermographers still exists, ready, as it has been since 1992, to be filled and used effectively in all applications.

In this paper we discuss the thermal properties of water as they relate to the structures, buildings in particular, thermographers routinely inspect. Interestingly, it is the unique thermal properties of water that allow us, under the right conditions, to locate its very presence in a building. Unfortunately, when conditions are less than ideal, water is often all but impossible to detect thermally. It is important then, to understand both the properties and behavior of this common substance as well as the conditions that cause it to be revealed. To this end we will also show examples of the interaction of water and heat and the surrounding materials as we observed them in several controlled situations. We will also apply the lessons learned to a wider variety of real world thermal imaging situations

Hyperactivition of an unwanted cellular cascade by the immune-related protein RNase L has been linked to reduced exercise capacity in persons with chronic fatigue syndrome (CFS). This investigation compares exercise capacities of CFS patients with deregulation of the RNase L pathway and CFS patients with normal regulation, while controlling for potentially confounding gender effects. Thirty-five male and seventy-one female CFS patients performed graded exercise tests to voluntary exhaustion. Measures of peak VO2, peak heart rate, body mass index, perceived exertion, and respiratory quotient were entered into a two-way factorial analysis with gender and immune status as independent variables. A significant multivariate main effect was found for immune status (p0.01), with no gender effect or interaction. Follow-up analyses identified VO2(peak) as contributing most to the difference. These results implicate abnormal immune activity in the pathology of exercise intolerance in CFS and are consistent with a channelopathy involving oxidative stress and nitric oxide-related toxicity.

Thermography is a powerful tool for locating or verifying levels in tanks and silos. But one could ask “Why bother?” All too often existing level indication instruments are simply not reliable or positive verification of instrumentation readings is required. When properly used, thermography can reveal not only the liquid/gas interface, but also sludge buildup and floating materials such as waxes and foams. Similar techniques can be used to locate levels and bridging problems in silos containing fluidized solids. This paper discusses the parameters and limitations that must be addressed, shows techniques that can be employed, and illustrates the discussions with numerous thermal images.

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800,000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the immune system. A symposium was organized in October 2001 to explore the possibility of an association between immune dysfunction and CFS, with special emphasis on the interactions between immune dysfunction and other abnormalities noted in the neuroendocrine and autonomic nervous systems of individuals with CFS. This paper represents the consensus of the panel of experts who participated in this meeting. Data suggest that persons with CFS manifest changes in immune responses that fall outside normative ranges, but current research does not provide definitive evidence on whether these immune abnormalities are a cause or result of the illness. It has become clear that CFS cannot be understood based on single measurements of immune, endocrine, cardiovascular, or autonomic nervous system dysfunction. This panel encourages a new emphasis on multidisciplinary research into CFS.

The biosynthesis of most biologically active peptides involves the action of prohomone convertases, including PC3 (also known as PC1), that catalyze limited proteolysis of precursor proteins. Proteolysis of prohormones occurs mainly in the granules of the regulated secretory pathway. It has been proposed that the targeting of these processing enzymes to secretory granules involves their association with lipid rafts in granule membranes. We now provide evidence for the interaction of the 86 and 64 kDa forms of PC3 with secretory granule membranes. Furthermore, both forms of PC3 were resistant to extraction with TX-100, were floated to low-density fractions in sucrose gradients, and were partially extracted upon cholesterol depletion by methyl-beta-cyclodextrin, indicating that they were associated with lipid rafts in the membranes. Protease protection assays, immunolabeling, and biotinylation of proteins in intact secretory granules identified an approximately 115-residue cytoplasmic tail for 86 kDa PC3. Using two-dimensional gel electrophoresis and a specific antibody, a novel, raft-associated form of 64 kDa PC3 that contains a transmembrane domain consisting of residues 619-638 was identified. This form was designated as 64 kDa PC3-TM, and differs from the 64 kDa mature form of PC3. We present a model of the membrane topology of PC3, where it is anchored to lipid rafts in secretory granule membranes via the transmembrane domain. We demonstrate that the transmembrane domain of PC3 alone was sufficient to target the extracellular domain of the IL2 receptor alpha-subunit (Tac) to secretory granules.

In familial hyperproinsulinemia, specific mutations in the proinsulin gene are linked with a profound increase in circulating plasma proinsulin levels. However, the molecular and cellular basis for this disease remains uncharacterized. Here we investigated how these mutations may disrupt the sorting signal required to target proinsulin to the secretory granules of the regulated secretory pathway, resulting in the unregulated release of proinsulin. Using a combination of molecular modeling and site-directed mutagenesis, we have identified structural molecular motifs in proinsulin that are necessary for correct sorting into secretory granules of endocrine cells. We show that membrane carboxypeptidase E (CPE), previously identified as a prohormone-sorting receptor, is essential for proinsulin sorting. This was demonstrated through short interfering RNA-mediated depletion of CPE and transfection with a dominant negative mutant of CPE in a β-cell line. Mutant proinsulins found in familial hyperproinsulinemia failed to bind to CPE and were not sorted efficiently. These findings provide evidence that the elevation of plasma proinsulin levels found in patients with familial hyperproinsulinemia is caused by the disruption of CPE-mediated sorting of mutant proinsulins to the regulated secretory pathway.

The purpose of this study was to examine physiological responses of persons with chronic fatigue syndrome (CFS) to a graded exercise test.Cardiopulmonary exercise tests were performed on 189 patients diagnosed with CFS. Based on values for peak oxygen consumption, patients were assigned to one of four impairment categories (none, mild, moderate, and severe), using American Medical Association (AMA) guidelines. A one-way MANOVA was used to determine differences between impairment categories for the dependent variables of age, body mass index, percentage of predicted [OV0312]O(2), resting and peak heart rates, resting and peak systolic blood pressure, respiratory quotient (RQ), and rating of perceived exertion.Significant differences were found between each impairment level for percentage of predicted [OV0312]O(2) and peak heart rate. Peak systolic blood pressure values for the "moderate," and "severe" groups differed significantly from each other and both other groups. The more impaired groups had lower values. The no impairment group had a significantly higher peak RQ than each of the other impairment levels (all P0.001). Peak [OV0312]O(2) values were less than predicted for all groups. Compared with the males, the women achieved actual values for peak [OV0312]O(2) that were closer to their predicted values.Despite a common diagnosis, the functional capacity of CFS patients varies greatly. Stratifying patients by function allows for a more meaningful interpretation of the responses to exercise and may enable differential diagnosis between subsets of CFS patients.

Thermography is widely used for inspecting electrical systems where costly problems are often preceded by telltale thermal signatures. Many thermographers, or their customers, however, mistakenly rely on radiometric temperature data to prioritize these findings. Due to the inherent limitations of radiometry and the complexities of heat transfer in the components being inspected, the data is all too often either inaccurate or misunderstood. Routinely, however, thermographers proceed as if nothing is amiss. This is due to an understandable, but misguided, attempt to simplify the decision-making process regarding repair priorities. The result is that predictions of repair priorities are not as accurate as they could be. On the one hand failures still occur while on the other repairs are often made inappropriately. In this paper we discuss the problems encountered when collecting and interpreting radiometric data. We will also outline a simple, effective system that thermographers are using to dramatically improve the predictive value of the technology. Improved results are achieved first separating the often intertwined questions of 'when will the component fail?' and 'what will be the consequences of failure?' The second improvement comes from incorporating all relevant data in the decision making process and weighing the impact each has. The system described, which can easily be adapted to diverse needs, is being used successfully and with repeatable results that have been shown to improve with usage.

The elevated RNase L enzyme activity observed in some Chronic Fatigue Syndrome (CFS) patients may be linked to the low exercise tolerance and functional impairment that typify this disease. The purpose of this investigation was to determine if specific indicators of physical performance can predict abnormal RNase L activity in CFS patients. Seventy-three CFS patients performed a graded exercise test to voluntary exhaustion. Forty-six patients had elevated RNase L levels. This measure was employed as the dependent variable in a discriminant function analysis, with peak V02, exercise duration and Karnofsky Performance Scores (KPS) serving as the independent variables. All three variables entered the single significant function (p0.001). The elevated RNase L group had a lower peak V02 and duration than the normal group, but a higher KPS. The results suggest that both exercise testing and the RNase L biomarker have potential to aid in the diagnosis of CFS.

Thermography has been used with great success for number of years to inspect building fenestration, both during design andproduction, as well as after installation. 1 Typically double-glazed windows exhibit a well-understood pattern of increasedheat loss around the perimeter, due mainly to thermal bridging or “edge-effect” losses.In this paper we present the findings of an investigation about a very different, and unusual, thermal pattern discovered onwindows in the home of one of the authors. The pattern was first illuminated by condensation in the central portion of thewindow. This thermal pattern was verified with a radiometric thermal imaging camera as well as thermal contact probes.After additional investigation we found the cause of this anomalous pattern is related to the loss of some of the insulatingargon gas installed in the window during manufacturing. We also discovered the problem was a not uncommon for certaintypes of windows. As these windows age, the problems usually become more pronounced and, in some cases, a total failureof the window by implosion results. We hope that publication of this information will prove useful to others who may havebeen mystified after seeing similar patterns.1. CONSTRUCTION OF INSULATING GLASS UNITSTypical insulating glass (IG) units are constructed using two sheets of window glass separated by spacers. The unit is sealedand filled with dry air or an inert gas. A desiccant is often installed in the spacer tominimize internal condensation of moisture. The exact design and placement ofthe spacers, sealants, and desiccants, as well as the specific type of insulating gasand fill technique used, may vary with the type, brand, and design needs of thewindow. Early IG units were rather crude by comparison to today’s high-performance fenestration although many continue to perform even after fiftyyears. Premature failures of sealants, in particular, were not uncommon, resultingin poor window performance and condensation forming between the panes ofglass.During the 1970s consumers began to demand windows that would be guaranteedto retain their seals for longer periods, typically 20 years. They also wantedwindows with better thermal performance in order to reduce energy use, increasecomfort levels, and improve condensation resistance.

The evolutionary trace (ET) method, a data mining approach for determining significant levels of amino acid conservation, has been applied to over 700 aligned G-protein-coupled receptor (GPCR) sequences. The method predicted the occurrence of functionally important clusters of residues on the external faces of helices 5 and 6 for each family or subfamily of receptors; similar clusters were observed on helices 2 and 3. The probability that these clusters are not random was determined using Monte Carlo techniques. The cluster on helices 5 and 6 is consistent with both 5,6-contact and 5,6-domain swapped dimer formation; the possible equivalence of these two types of dimer is discussed because this relates to activation by homo- and heterodimers. The observation of a functionally important cluster of residues on helices 2 and 3 is novel, and some possible interpretations are given, including heterodimerization and oligomerization. The application of the evolutionary trace method to 113 aligned G-protein sequences resulted in the identification of two functional sites. One large, well-defined site is clearly identified with adenyl cyclase, beta/gamma and regulator of G-protein signaling (RGS) binding. The other G-protein functional site, which extends from the ras-like domain onto the helical domain, has the correct size and electrostatic properties for GPCR dimer binding. The implications of these results are discussed in terms of the conformational changes required in the G-protein for activation by a receptor dimer. Further, the implications of GPCR dimerization for medicinal chemistry are discussed in the context of these ET results.

A β-turn overlay hypothesis has been used to transform the core scaffold of a selective non-peptide bradykinin B 2 receptor antagonist into ligands specifically recognized by the CCK 2 or NK 1 receptors.

Thermographers are often at risk when inspecting electrical systems. While electrocution is always a hazard, a far greater danger is injury associated with accidental exposure to an arc flash explosion. Because of the potential for serious injury, and because of new government regulations, more and more companies are now taking steps to prevent arc flash injury and to minimize damage if and when it does occur. In this paper, which would not have been possible without the able assistance of Lowry Eads, global resource for infrared thermography in Dupont, I will discuss why arc flash explosions happen and what damage they can do; I will also show how thermographers can both reduce their risk of being exposed to one and, if they are exposed, their injury from the explosion.

Inspecting compression splices on transmission and distribution lines has long been accomplished using infrared thermography but the results have too often been disappointing. There are instances of splices failing within months ofinfrared inspections. An understanding of the actual condition of the splices had been "masked" by one or more of the factors discussed in this paper. A number of factors are involved, including a poor understanding of the application of the technology; inadequate training of some service providers; environmental factors; low electrical loading; the resolutionlimitations of the inspection equipment; low emissivity of the components, and a poor understanding of how to interpret thedata.The result has been that too often the severity of found problems has been underestimated and some problems have simplynot been located. As electrical utilities restructure themselves in a deregulated environment, they will require a much higherlevel of assurance of reliability.This paper discusses the background for using thermography in the industry and the results that have been had in the past. Italso details steps that can be taken to improve these results to provide for greater confidence in the interpretation of the datacollected.Keywords: ASNT, compression splice, electrical, electrical utilities, emissivity, infrared, predictive maintenance, T&D,thermography, transmission line1.0 OVERVIEW OF THE NEED FOR BETTER INSPECTIONS

Bradyzide is from a novel class of rodent-selective non-peptide B(2) bradykinin antagonists (1-(2-Nitrophenyl)thiosemicarbazides). Bradyzide has high affinity for the rodent B(2) receptor, displacing [(3)H]-bradykinin binding in NG108-15 cells and in Cos-7 cells expressing the rat receptor with K(I) values of 0.51+/-0.18 nM (n=3) and 0.89+/-0.27 nM (n=3), respectively. Bradyzide is a competitive antagonist, inhibiting B(2) receptor-induced (45)Ca efflux from NG108-15 cells with a pK(B) of 8.0+/-0.16 (n=5) and a Schild slope of 1.05. In the rat spinal cord and tail preparation, bradyzide inhibits bradykinin-induced ventral root depolarizations (IC(50) value; 1.6+/-0.05 nM (n=3)). Bradyzide is much less potent at the human than at the rodent B(2) receptor, displacing [(3)H]-bradykinin binding in human fibroblasts and in Cos-7 cells expressing the human B(2) receptor with K(I) values of 393+/-90 nM (n=3) and 772+/-144 nM (n=3), respectively. Bradyzide inhibits bradykinin-induced [(3)H]-inositol trisphosphate (IP(3)) formation with IC(50) values of 11.6+/-1.4 nM (n=3) at the rat and 2.4+/-0.3 microM (n=3) at the human receptor. Bradyzide does not interact with a range of other receptors, including human and rat B(1) bradykinin receptors. Bradyzide is orally available and blocks bradykinin-induced hypotension and plasma extravasation. Bradyzide shows long-lasting oral activity in rodent models of inflammatory hyperalgesia, reversing Freund's complete adjuvant (FCA)-induced mechanical hyperalgesia in the rat knee joint (ED(50), 0.84 micromol kg(-1); duration of action4 h). It is equipotent with morphine and diclofenac, and 1000 times more potent than paracetamol, its maximal effect exceeding that of the non-steroidal anti-inflammatory drugs (NSAIDs). Bradyzide does not exhibit tolerance when administered over 6 days. In summary, bradyzide is a potent, orally active, antagonist of the B(2) bradykinin receptor, with selectivity for the rodent over the human receptor. British Journal of Pharmacology (2000) 129, 77 - 86

Health care institutions across the country have implemented internal compliance review processes. Few, however, are consistent or powerful enough. With physician support, rigorous research and fair disciplinary action, internal reviews can be improved. A 12-step procedure can smooth issue resolution.

The American Society of Nondestructive Testing (ASNT) has recently established a new central certification program. This program will allow individuals who meet the requirements to receive a 'portable' certificate. Augmenting the existing employer-based certification, this program will have significant impact on industries that may ultimately require nondestructive testing (NDT) personnel to have central certification. This paper explains show ASNT has structured central certification and when and how it will effect thermal/infrared thermography (T/IRT) personnel. The paper also discusses the industry specific certification process.© (1997) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

The Snell & Wilcox Group in the mid 1990s is a far cry from what it was 10 years ago. With the fusion of the original Snell and Wilcox, Electrocraft Consultants, and CEL, the Snell and Wilcox Group boasts a total of 81 company-years of video equipment experience (including digital image processors, standards convertors and TV equipment). The author discusses the evolution of the Snell & Wilcox Group through its constituent companies from the 1960s to the present. (5 pages)

8114 Background: In EGFR-TKI responsive NSCLC, at progression only some tumor clones might carry resistance mechanisms. This provides a rationale for maintenance therapy with TKIs on progression and is supported by “tumor flares” noted in patients taken off of TKI therapy. Methods: Randomized, phase II study of chemotherapy (pemetrexed or docetaxel) versus chemotherapy plus erlotinib (ERL) in patients with progressive NSCLC following clinical benefit from erlotinib for > 12 weeks. In Arm A Pemetrexed or Docetaxel were given at standard doses every 3 weeks to a maximum of 8 cycles. In Arm B chemotherapy was given with ERL at 150 mg oral daily dose on days 2-19 of each cycle. The primary endpoint was that continuation ERL in this patient population could extend PFS by 50%, from 3 to 4.5 months. The original enrollment goal was 39 pts per arm to allow 80% power to detect such a difference. Results: 46 patients were randomized (Arm A: 24; Arm B: 22). Early termination was due to slow enrollment. Patient characteristics were well balanced except for more females on Arm A (p=0.075). The median PFS on Arm A was 5.4 months and for Arm B was 4.6 months (p=0.569). The median overall survival (OS) on Arm A was 18.7 months and for Arm B 14.7 months (p=0.295). Multiple Cox regression analysis showed an impact of female gender on OS (HR 0.1) but not PFS (HR=0.49). EGFR status was available on 39/46 patients. 17 patients in Arm A and 14 Arm B were mutation positive. In analyzing mutation + only patients, no difference in PFS (p=0.332) or OS (p=0.346) was seen amongst the 2 groups. In the mutation + patients the 6 months PFS for Arm A was 39% and for Arm B was 32%. More toxicity was seen on Arm B as compared to Arm A. Irrespective of causal attribution, 1 grade 5 event occurred on Arm A as opposed to 2 events on Arm B. A total of 7 grade 3/4 events occurred on Arm A while 24 occurred on Arm B. Conclusions: No benefit was seen with the continuation of ERL in addition to chemotherapy as compared to chemotherapy alone in patients who had previously benefited from ERL but then showed progression. The combination arm showed significantly more toxicity. Clinical trial information: NCT00660816.

Hydraulic systems are the life blood of many industrial processes, especially the manyforming presses used in the automotive industry. The loss of a press due to a hydraulic systemfailure can be very expensive, both in terms of reduced machine availability and diminishedproduct quality. Thermography has proven to be an excellent maintenance inspection toolbecause the performance of hydraulic systems are easily characterized by their thermalsignatures. Thermography also provides instantaneous, real time thermal data which is essentialto understanding a dynamic system like hydraulics. This paper, based on many of Milan Plastics'six years of experience with hydraulic systems, outlines the key components that can beinspected with thermography and discusses problems that are typically found.Keywords: ASNT, hydraulic systems, infrared, maintenance, predictive maintenance,thermography2. INTRODUCTIONHydraulic systems do work by using a liquid, typically oil, pressurized by a pump, totransfer power and displace a piston. A typical hydraulic machine is made up of manycomponents, including, among others, pumps, motors, cylinders, heat exchangers, filters, andvalves. The valves, which are often mounted on a manifold, can be of several types, includingcheck valves, relief valves, pressure reducing valves, 4-way valves, manual valves, and servovalves. Figure 1 shows a typical hydraulic machine.

Written inspection procedures are an essential element of acquiring valid data on a repeatable basis. They are also vital to the safety of the thermographer, and may, for that reason alone, be required by a company or regulatory agencies. Many thermographers are working with either no procedures or procedures that have not been developed specifically to meet their needs. To date only a few of the necessary procedures have been developed by recognized standards organizations. The lack of procedures is limiting the use of thermography. Where the technology is being used without procedures, results are often less than optimum. This paper (1) surveys existing procedures and standards; (2) discusses current efforts by standards organizations to develop standards and procedures; and (3) presents a general methodology from which written inspection procedures can be developed for many thermographic inspections.© (1996) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Background The presence of antiphospholipid antibodies has been associated with thrombotic events in systemic lupus erythematosus and other diseases. Antiphosphatidylserine antibodies have been shown more recently to have clinical implications being noted in thrombocytopenia, positive VDRL test, prolonged partial thromboplastin time, and recurrent fetal loss. Objective To report a patient with systemic lupus erythematosus who presented with a myocardial infarction resulting from a single clot in the distal left anterior descending coronary artery and to discuss the merits of evaluating such patients for the presence of antiphospholipid antibodies. Methods Case report and review of the literature. Results A 55-year-old woman with no risk factors for coronary artery disease presented with a myocardial infarction. A distal left anterior descending coronary artery clot was seen on angiography. Evaluation for the presence of a hypercoagulable state revealed evidence for systemic lupus erythematosus. Although lupus anti-coagulant and anticardiolipin antibody titers were negative, antiphosphatidylserine IgA antibodies were detected. Conclusion Because antiphosphatidylserine antibodies of the IgA isotype have been shown to be associated with thrombosis and other manifestations of systemic lupus erythematosus, a complete evaluation for antiphospholipid antibodies should include testing for all three isotypes.

A sorting signal which directs the prohormone pro-opiomelanocortin (POMC) to the regulated secretory pathway was identified. This sorting signal motif consists of a 13 amino acid (POMC8–20) amphipathic loop stabilized by a disulfide bridge (Cys8–Cys20) located at the N-terminus of pro-opiomelanocortin. It binds at an acidic pH specifically to an ~64 kD sorting receptor protein present in Golgi and secretory granule membranes of neuroendocrine cells. These findings support the hypothesis that pro-opiomelanocortin is targeted to the regulated secretory pathway by a receptor-mediated mechanism.

The B 2 bradykinin receptor purified from rat uterus has an apparent molecular mass of 81 kDa. This is higher than the value of 42 kDa estimated from the sequence data of rat and human B 2 receptors. Carbohydrate analysis of the rat B 2 bradykinin receptor indicated that it was a sialoglycoprotein with three N-linked complex oligosaccharide side chains. This was consistent with the sequence, which has three potential glycosylation sites. The receptor did not appear to possess O-linked carbohydrate side chains. Removal of the N-linked carbohydrates with endo-β-N-acetylglucosaminidase yielded a core protein of 42-44 kDa. The presence of these N-linked carbohydrates explains the discrepancy between the molecular size of the purified receptor protein and that estimated from the sequence. The sequence of the rat receptor suggests an isoelectric point of about pH 7.0, but the purified receptor had an isoelectric point of pH 4.5-4.7. Sialic acid residues on the N-linked side chains are likely to be responsible for the acidic nature of the rat receptor. Carbohydrate does not appear to play a role in ligand-receptor interactions, as deglycosylation did not alter the affinity of the B 2 bradykinin receptor for bradykinin or the B 2 -selective antagonist HOE-140.

The NH2-terminal region of pro-opiomelanocortin (POMC) is highly conserved across species, having two disulfide bridges that cause the formation of an amphipathic hairpin loop structure between the 2nd and 3rd cysteine residues (Cys8 to Cys20). The role that the NH2-terminal region of pro-opiomelanocortin plays in acting as a molecular sorting signal for the regulated secretory pathway was investigated by using site-directed mutagenesis either to disrupt one or more of the disulfide bridges or to delete the amphipathic loop entirely. When POMC was expressed in Neuro-2a cells, ACTH immunoreactive material was localized in punctate secretory granules in the cell body and along the neurites, with heavy labeling at the tips. ACTH was secreted from these POMC-transfected cells in a regulated manner. Disruption of both disulfide bridges or the second disulfide bridge or removal of the amphipathic hairpin loop resulted in constitutive secretion of the mutant POMC from the cells and a lack of punctate secretory granule immunostaining within the cells. We have modeled the NH2-terminal POMC Cys8 to Cys20 domain and have identified it as an amphipathic loop containing four highly conserved hydrophobic and acidic amino acid residues (Asp10-Leu11-Glu14-Leu1). Thus the sorting signal for POMC to the regulated secretory pathway appears to be encoded by a specific conformational motif comprised of a 13-amino acid amphipathic loop structure stabilized by a disulfide bridge, located at the NH2 terminus of the molecule.

The primary value of using infrared thermography to inspect electrical systems is to find problems made apparent by their thermal differences. Thermographers have also begun collecting radiometric temperature data as quantitative imaging systems have become more reliable and portable. Throughout the industry the use of temperature data has become a primary means of prioritizing the severity of a problem. The validity of this premise is suspect for several reasons, including the lack of standard data collection methods; the often poor understanding of radiometric measurements by maintenance thermographers; field conditions that vary widely enough to defy standardization; and the almost total lack of scientific research on the relationship between heat and time with regard to the failure of the components being inspected. Several possible solutions to the problems raised, as well as other suggestions for improving the usefulness and reliability of qualitative inspections, are offered.