Variants of human chorionic gonadotropin from pregnant women and tumor patients recognized by monoclonal antibodies

In biological fluids, hCG and its free alpha- (hCG alpha) and beta-subunits (hCG beta), occur in multiple forms. These various forms differ at the molecular level primarily in glycosylation, but also differ in protein backbone modifications corresponding to the urinary low molecular weight fragment of the hCG beta-subunit (beta-core fragment). This microheterogeneous nature can be demonstrated by isoelectric focusing in which variants are separated into bands with different isoelectric points (pI). To determine whether such isoelectric variants differ in antigenicity and consequently might escape immunoassay detection due to overspecificity of monoclonal antibodies (MCA), urinary pregnancy hCG (NIH, CR123) and tumor hCG preparations, such as a tumor-specific acidic variant of hCG (hCGav) and the hCG beta-core fragment, were separated by isoelectric focusing in the absence or presence of 8 M urea, or by sodium docedyl sulfate-polyacrylamide gel electrophoresis and enzymatically immunostained using an MCA panel directed against 17 different hCG epitopes. MCA against 14 different epitopes accessible on holo-hCG recognized all pI variants of pregnancy holo-hCG or tumor-derived hCGav, as was true for the three MCA recognizing epitopes hidden on holo-hCG but accessible on the free subunits after hCG dissociation by urea. We conclude that each individual pI-isoform of holo-hCG and its free subunits expresses the entire set of epitopes recognized by our MCA panel. The carbohydrate moieties that form a biochemical basis for hCG heterogeneity seem to be neither of major antigenic relevance, nor are they structurally related to any particular epitope. Thus, various glycosylation forms of hCG, hCG alpha, hCG beta, and hCG beta-core in normal as well as in pathological samples should safely be detectable and measureable by immunoassays employing MCA with appropriate subunit specificity

Technical Note: Comparison of storage strategies of sea surface microlayer samples

The sea surface microlayer (SML) is an important biogeochemical system whose physico-chemical analysis often necessitates some degree of sample storage. However, many SML components degrade with time so the development of optimal storage protocols is paramount. We here briefly review some commonly used treatment and storage protocols. Using freshwater and saline SML samples from a river estuary, we investigated temporal changes in surfactant activity (SA) and the absorbance and fluorescence of chromophoric dissolved organic matter (CDOM) over four weeks, following selected sample treatment and storage protocols. Some variability in the effectiveness of individual protocols most likely reflects sample provenance. None of the various protocols examined performed any better than dark storage at 4 °C without pre-treatment. We therefore recommend storing samples refrigerated in the dark

Immunoreactive human chorionic gonadotropin and its free ß-subunit in serum and ascites of patients with malignant tumors

Human chorionic gonadotropin (hCG) is a clinically relevant marker of trophoblastic and nontrophoblastic malignancies. In the present studies, in addition to determining serum hCG, we investigated the presence and properties of hCG immunoreactivity in ascites of patients with nontrophoblastic malignant tumors and, for comparison, in ascites caused by cirrhotic liver disease. Total hCG immunoreactivity [hCG (+hCG-ß)] was found to be elevated above the reference value (>5 IU/liter) in the serum of 2 of 20 patients with cirrhosis and 11 of 20 patients with malignant tumors. For comparison, in ascites, hCG (+hCG-ß) concentrations were frequently higher than in the corresponding serum samples and exceeded 10 IU/liter in 0 of 20 cirrhotic samples and in 16 of 20 malignant samples. In order to elucidate the nature of the hCG immunoreactive material, all samples were then assessed by immunoradiometric assays specific for the intact hCG molecule (holo-hCG) and the free hCG-ß subunit, respectively. In the holo-hCG assay, elevated values were detected in 0 of 20 (0 of 20) cirrhotic ascites (serum) samples and 0 of 20 (1 of 20) malignant ascites (serum) samples. In the free hCG-ß assay, on the other hand, no positive results were obtained in the ascites or serum of 20 patients with liver cirrhosis; however, 8 of 20 serum samples and 16 of 20 ascites samples derived from tumor patients were positive. In accord with the immunological data, gel chromatographical studies of malignant ascites revealed the abundance of free hCG-ß subunit rather than that of holo-hCG. In contrast to malignancy-related ascites, in ascites of patients receiving hCG injections for treatment of infertility, holo-hCG was more abundant than free hCG-ß immunoreactivity. Incubation experiments of purified holo-hCG in ascites for 24 h at -20, 20, or 37°C showed no substantial dissociation of the hCG molecule and release of free hCG-ß immunoreactivity, thus arguing against production of free hCG-ß by degradation of holo-hCG and in favor of its tumor-related secretion. In conclusion, hCG-ß immunoreactivity is frequently elevated in malignancy-related ascites and appears to be related to the presence of free ß subunit of hCG rather than that of the intact hCG molecule. Interestingly, hCG-ß determination in ascites proved to be clearly superior to serum measurement in discriminating between tumor and cirrhosis. Thus, hCG-ß might be a useful marker of malignancy-related ascites and should be prospectively assessed for possible clinical use in comparison with other well-established parameters, such as cytology and protein determination. For this purpose, according to our results, only assays that exhibit a high sensitivity for free hCG-ß subunit appear to be suitable

Flow tilt angles near forest edges - Part 1: Sonic anemometry

An analysis of flow tilt angles from a fetch-limited beech forest site with clearings is presented in the context of vertical advection of carbon dioxide. Flow angles and vertical velocities from two sonic anemometers by different manufacturers were analyzed. Instead of using rotations, where zero-flow angles were assumed for neutral flow, the data was interpreted in relation to upstream and downstream forest edges. <br><br> Uncertainties caused by flow distortion, vertical misalignment and limited sampling time (statistical uncertainty) were evaluated and found to be highly significant. Since the attack angle distribution of the wind on the sonic anemometer is a function of atmospheric stratification, an instrumental error caused by imperfect flow distortion correction is also a function of the atmospheric stratification. In addition, it is discussed that the sonic anemometers have temperature dependent off-sets. These features of the investigated sonic anemometers make them unsuitable for measuring vertical velocities over highly turbulent forested terrain. By comparing the sonic anemometer results to that of a conically scanning Doppler lidar (Dellwik et al., 2010b), sonic anemometer accuracy for measuring mean flow tilt angles was estimated to between 2° and 3°. Use of planar fit algorithms, where the mean vertical velocity is calculated as the difference between the neutral and non-neutral flow, does not solve this problem of low accuracy and is not recommended. <br><br> Because of the large uncertainties caused by flow distortion and vertical alignment, it was only possible to a limited extent to relate sonic anemometer flow tilt angles to upwind forest edges, but the results by the lidar indicated that an internal boundary layer affect flow tilt angles at 21m above the forest. This is in accordance with earlier studies at the site. <br><br> Since the mean flow tilt angles do not follow the terrain, an estimate of the vertical advection term for near-neutral conditions was calculated using profile measurements of carbon dioxide. The estimated advection term is large, but it is not recommended to include it in the surface carbon balance, unless all terms in the carbon dioxide conservation equation can be precisely estimated

N-body Gravity and the Schroedinger Equation

We consider the problem of the motion of $N$ bodies in a self-gravitating system in two spacetime dimensions. We point out that this system can be mapped onto the quantum-mechanical problem of an N-body generalization of the problem of the H$_{2}^{+}$ molecular ion in one dimension. The canonical gravitational N-body formalism can be extended to include electromagnetic charges. We derive a general algorithm for solving this problem, and show how it reduces to known results for the 2-body and 3-body systems.Comment: 15 pages, Latex, references added, typos corrected, final version that appears in CQ

Preventive health risk appraisal for older people and impact on GPs' patient management: a prospective study

Background. Health risk appraisals (HRAs) are recommended for detection of potentially modifiable risk factors for health status decline of older people. Little is known how family physicians manage detected risk factors. Objective. We evaluated (i) if risk factors in one or more of five predefined domains were detected in a primary care-based HRA and (ii) how often these findings had an impact on the further management of patients. Methods. We performed a prospective observational study in a rural community in Austria and included persons (age ≥ 70 years) living at home. We applied the standardized assessment for elderly people in primary care (STEP) instrument and evaluated risk factors for status decline assessing five domains (cognitive function, depression, urinary incontinence, hearing impairment and mobility/falls). Results. Two hundred and sixty-four persons participated and the HRA revealed a wide range of risk factors for health status decline [from 4.5% (12/264) in the depression domain up to 31% (81/264) for mobility/falls and 41% (107/264) in the cognitive domain]. The findings had an impact on the further management in four domains: hearing impairment (100% of findings with impact), mobility/falls (93%), depression (83%) and urinary incontinence (65%). In contrast, abnormal cognitive findings lead to action only in every fifth participant (18%; 19/107). Conclusion. In contrast to other domains, family physicians are hesitant to act upon abnormal findings of cognitive testing. Additional knowledge is needed to clarify the value of abnormal cognitive findings for management of patients and support of their carer

Movement Patterns Used by the Elderly When Getting Out of Bed

Background and Purpose. Getting out of bed is difficult for 27.6% of people over 65. The purpose of this study is to describe movement patterns used by older adults for rising from bed. Subjects. 42 healthy subjects between the ages of 65 and 90. Methods. Subjects were videotaped performing 5 trials of getting out of bed. Movement patterns were categorized for each body part. Results. A number of movement patterns occurred that were not reported in younger people. The most frequent movement patterns used were: “roll off” (38.3%) for the trunk, “double push” (34.7%) for the far arm, “multi-push” (36.0%) for the near arm, and “synchronous” (31.2%) for the legs. Discussion and Conclusion. A variety of movement patterns are used by older people for rising from bed. Movement patterns described in this study can be used as a guide for physical therapists and occupational therapists in teaching age-appropriate strategies for getting out of bed

Feature-Model-Guided Online Learning for Self-Adaptive Systems

A self-adaptive system can modify its own structure and behavior at runtime based on its perception of the environment, of itself and of its requirements. To develop a self-adaptive system, software developers codify knowledge about the system and its environment, as well as how adaptation actions impact on the system. However, the codified knowledge may be insufficient due to design time uncertainty, and thus a self-adaptive system may execute adaptation actions that do not have the desired effect. Online learning is an emerging approach to address design time uncertainty by employing machine learning at runtime. Online learning accumulates knowledge at runtime by, for instance, exploring not-yet executed adaptation actions. We address two specific problems with respect to online learning for self-adaptive systems. First, the number of possible adaptation actions can be very large. Existing online learning techniques randomly explore the possible adaptation actions, but this can lead to slow convergence of the learning process. Second, the possible adaptation actions can change as a result of system evolution. Existing online learning techniques are unaware of these changes and thus do not explore new adaptation actions, but explore adaptation actions that are no longer valid. We propose using feature models to give structure to the set of adaptation actions and thereby guide the exploration process during online learning. Experimental results involving four real-world systems suggest that considering the hierarchical structure of feature models may speed up convergence by 7.2% on average. Considering the differences between feature models before and after an evolution step may speed up convergence by 64.6% on average. [...