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For research involving customary land rights, ‘context is key’ because every context brings specific nuances for consideration. Failure to account for context runs the risk of irrelevance, unintended consequences and/or failure. We present a research method that allows context to speak: the progressive case study. The approach combines deductive case study with inductive grounded theory approaches. The results are used to propose a framework for guiding cadastral systems development in customary land rights contexts. This paper presents the methodology, which should be useful for researchers, NGOs and multinational organisations doing development programming in developing contexts.

Substantial inconsistency exists in the effectiveness of existing interventions to improve heart failure (HF) self-care, which can be partially explained by the fact that self-management interventions often lack theoretical models that underpin intervention development. The COM-B behavior model is a comprehensive theoretical framework that can be used to develop effective, theory-based interventions. The aim of this article is to highlight the challenges and practical solutions when applying the COM-B model to HF self-care, in order to provide useful support for researchers intending to use the model for designing behavior change interventions. “The Behaviour Change Wheel” handbook provides a step-by-step guide to understand and change behavior. When following the guide, some practical and methodological challenges were encountered. Lessons learnt to overcome these challenges are reported. Although the handbook is a comprehensive guide for designing behavior change interventions, a number of challenges arose. For example, the descriptions provided in the guide were not always sufficient to make solid judgments on how to categorize determinants; narrowing down intervention possibilities to a manageable number and prioritizing potential behavior change techniques over others involved a certain amount of subjectivity in an otherwise highly systematic and structured approach. For the encountered challenges, solutions are provided to illustrate how the model was applied practically to design theory-based behavior change interventions. This article provides a useful reference for researchers’ use of the COM-B behavior model, as it outlines challenges that may occur and potential solutions to overcome them.This article documents the process of using the Behaviour Change Wheel guide to design a heart failure self-care intervention and the decisions we had to make to fill in the missing information the guide does not provide.

A broad-based interlaboratory study of glycosylation profiles of a reference and modified IgG antibody involving 103 reports from 76 laboratories.

Land reform in South Africa has failed to meet its objectives. The intended beneficiaries often do not have their land reform needs met. Failures may be attributed to multiple sources. We propose a conceptual framework to assist governments conducting land reform projects. It draws on aspects of human rights, good governance, and pro-poor policy. Existing frameworks are combined with these aspects to derive the conceptual framework. By using the framework, development projects in South Africa and similar contexts may become more Successful, Sustainable, and Significant. The paper holds interest for land tenure and cadastral systems researchers and developers.

The Ring of Truth The Wisdom of Wagner's Ring of the Nibelung By Roger Scruton Allen Lane, HB, 401pp,25 £ ISBN 978-0-241-18855-2 However determinedly musicologists try to confine the serious [...]

If you don't know Mariko Tamaki, I'd like to introduce you. The whip-smart, stylish 32-year-old wears many glittery crowns while bombing around on her scooter through the streets of her [...]

Sarah Waters is much smaller and more composed than I'd imagined--from her epic novels I expected her to be wild-eyed, full of non sequitors and dramatic hair tosses. But, alas, [...]

PRIOR TO 2006, the primary unmet health care need for retirees was coverage of prescription drugs. Up to this point, Medicare provided retirees with coverage for most other acute care [...]

One of the principal goals of glycoprotein research is to correlate glycan structure and function. Such correlation is necessary in order for one to understand the mechanisms whereby glycoprotein structure elaborates the functions of myriad proteins. The accurate comparison of glycoforms and quantification of glycosites are essential steps in this direction. Mass spectrometry has emerged as a powerful analytical technique in the field of glycoprotein characterization. Its sensitivity, high dynamic range, and mass accuracy provide both quantitative and sequence/structural information. As part of the 2012 ABRF Glycoprotein Research Group study, we explored the use of mass spectrometry and ancillary methodologies to characterize the glycoforms of two sources of human prostate specific antigen (PSA). PSA is used as a tumor marker for prostate cancer, with increasing blood levels used to distinguish between normal and cancer states. The glycans on PSA are believed to be biantennary N-linked, and it has been observed that prostate cancer tissues and cell lines contain more antennae than their benign counterparts. Thus, the ability to quantify differences in glycosylation associated with cancer has the potential to positively impact the use of PSA as a biomarker. We studied standard peptide-based proteomics/glycomics methodologies, including LC-MS/MS for peptide/glycopeptide sequencing and label-free approaches for differential quantification. We performed an interlaboratory study to determine the ability of different laboratories to correctly characterize the differences between glycoforms from two different sources using mass spectrometry methods. We used clustering analysis and ancillary statistical data treatment on the data sets submitted by participating laboratories to obtain a consensus of the glycoforms and abundances. The results demonstrate the relative strengths and weaknesses of top-down glycoproteomics, bottom-up glycoproteomics, and glycomics methods.

Two identical new instruments, the Sutherland High-speed Optical Cameras (SHOC), have been developed for use on the South African Astronomical Observatory's (SAAO) 1.9, 1.0 and 0.75 m telescopes at Sutherland. The SHOC systems are fast-frame-rate, accurately-timed, high-quality, visible-wavelength imagers. Each system consists of a camera, global positioning system (GPS), control computer and peripherals. The primary component is an Andor iXon X3 888 UVB camera, utilizing a 1024 × 1024 pixel, frame-transfer, thermoelectrically-cooled, back-illuminated CCD. One of SHOC's most important features is that it can achieve frame rates of between 1 and 20 frames/s during normal operation (dependent on binning and subframing) with microsecond timing accuracy on each frame (achieved using frame-by-frame GPS triggering). Frame rates can be increased further, and fainter targets observed, by making use of SHOC's electron-multiplying (EM) modes. SHOC is therefore ideally suited to time domain astronomy where high frame rates and extremely accurate timing are critical. Here, we present details of the instrument components, characteristics measured during commissioning, science demonstrations, and development plans. Attention is specifically given to exploration of the signal-to-noise (S/N) parameter space as a function of EM and conventional modes. These results enable observers to optimize instrumental settings for their observations and clearly demonstrate the advantages and potential pitfalls of the EM modes.

The steroidogenic enzyme 3-β hydroxysteroid dehydrogenase 2 (3βHSD2) mediates the conversion of pregnenolone to progesterone and dehydroepiandrosterone to androstenedione through both its dehydrogenase and isomerase activities, making it necessary for the protein to undergo a reversible conformational change. We hypothesized that chaperones assist 3βHSD2 in switching between the conformations to initiate, enhance, and maintain activity. In the presence of the chaperone lauryl maltoside (LM), 3βHSD2 immediately converted pregnenolone to progesterone, with a 6.4-fold increase in synthesis. Using far-UV circular dichroism (CD), we found that addition of LM increased 3βHSD2’s α-helical content, which over time reverted to control levels, suggesting the formation of a stable but reversible conformation possibly due to hydrophobic interactions of the protein with LM micelles. We also found that LM increased fluorescence resonance energy transfer (FRET) about 11-fold between 3βHSD2 and fluorescing ANS molecules. This observation supports the idea that detergent(s) act as chaperones to assist 3βHSD2 in forming stable complexes, which in turn promotes proper folding. Mass spectrometric fingerprinting illustrated that LM incubation resulted in an ordered fragmentation of molecular mass from 39 to 13 kDa, as compared to limited or no proteolysis in the absence of LM. In addition, space-filling modeling demonstrated that 3βHSD2 association with detergents likely exposed the hydrophobic region, leading to its proteolysis. We conclude that detergents help 3βHSD2 to refold in order to rejuvenate, contributing to the ability of cells to rapidly produce steroids when needed.

Steroidogenic acute regulatory protein facilitates the translocation of cholesterol to the inner mitochondrial membrane, thereby initiating steroidogenesis. At the inner mitochondrial membrane, cytochrome P450 side-chain cleavage enzyme converts cholesterol to pregnenolone, an oxidative process requiring electrons from NADPH. Pregnenolone then serves as the substrate for the formation of progesterone or dehydroepiandrosterone by downstream enzymes. Studies have shown that cigarette smoke (CS) influences steroid hormone levels. To better understand the underlying mechanisms, we used a mouse model to study the effects of chronic CS exposure on steroidogenesis. Through radioimmunoassay and metabolic conversion assays, we found that CS reduced progesterone and dehydroepiandrosterone without affecting cytochrome P450 side-chain cleavage enzyme or 3β-hydroxysteroid dehydrogenase 2 expression. However, CS did reduce expression of cytochrome c oxidase IV (COX IV), a component of the mitochondrial complex that serves as the last enzyme in the electron transport chain. Small interfering RNA-mediated COX IV knockdown indeed decreased progesterone synthesis in steroidogenic cells. In summary, COX IV likely plays a role in steroidogenesis, and passive smoking may negatively affect steroidogenesis by disrupting the electron transport chain.

We recently reported that matrix metal‐loproteinase 2 (MMP‐2, gelatinase A) cleaves big endo‐thelin 1 (ET‐1), yielding the vasoactive peptide ET‐1[1–32]. We tested whether ET‐1[1–32] could affect the adhesion of human neutrophils to coronary artery endothelial cells (HCAEC). ET‐1[1–32] rapidly down‐regulated the expression of L‐selectin and up‐regulated expression of CD11b/CD18 on the neutrophil surface, with EC50values of 1–3 nM. These actions of ET‐1[1–32] were mediated via ETAreceptors and did not require conversion of ET‐1[1–32] into ET‐1 by neutrophil proteases, as revealed by liquid chromatography and mass spectroscopy. Moreover, ET‐1[1–32] evoked release of neutrophil gelatinase B, which cleaved big ET‐1 to yield ET‐1[1–32], thus revealing a positive feedback loop for ET‐1[1–32] generation. Up‐regula‐tion of CD11b/CD18 expression and gelatinase release was tightly associated with activation of extracellular signal‐regulated kinase (Erk). Stimulation of Erk activity was due to activation of Ras, Raf‐1, and MEK (MAPK kinase). ET‐1[1–32] also produced slight increases in the expression of ICAM‐1 and E‐selectin on HCAEC, and markedly enhanced ß2integrin‐dependent adhesion of neutrophils to activated HCAEC. These results are the first indication that gelatinolytic MMPs via cleavage of big ET‐1 to yield ET‐1[1–32] activate neu‐trophils and promote leukocyte‐endothelial cell adhesion and, consequently, neutrophil trafficking into inflamed tissues.—Fernandez‐Patron, C., Zouki, C., Whittal, R., Chan, J. S. D., Davidge, S. T., Filep, J. G. Matrix metalloproteinases regulate neutrophil‐endothelial cell adhesion through generation of endothelin‐ 1[1–32]. FASEB J.15, 2230–2240 (2001)

Tetanus toxin belongs to a family of clostridial protein neurotoxins for which there are no known antidotes. Another closely related member of this family, botulinum toxin, is being used with increasing frequency by physicians to treat severe muscle disorders. Botulinum toxin has also been produced in large quantities by terrorists for use as a biological weapon. To identify small molecule ligands that might bind to the targeting domain of tetanus and botulinum toxins and to facilitate the design of inhibitors and new reagents for their detection, molecular docking calculations were used to screen a large database of compounds for their potential to bind to the C fragment of tetanus toxin. Eleven of the predicted ligands were assayed by electrospray ionization mass spectrometry (ESI-MS) for binding to the tetanus toxin C fragment, and five ligands (45%) were found to bind to the protein. One of these compounds, doxorubicin, was observed to have strong hydrophobic interactions with the C fragment. To check the ligands for their ability to compete with ganglioside binding, each was also tested using a GT1b liposome assay. Doxorubicin was the only ligand found to competitively bind the tetanus toxin C fragment with an appreciable binding constant (9.4 μM).

Although the ionization/desorption mechanisms in matrix-assisted laser desorption/ionization (MALDI) remain poorly understood, there is a clear difference between the energy absorption processes in the ultraviolet (UV) and infrared (IR) modes of operation. UV-MALDI demands an on-resonance electronic transition in the matrix compound, whereas results presented here support earlier work showing that a corresponding resonant vibrational transition is not a requirement for IR-MALDI. In fact, data from the present study suggest that significant absorption of radiant energy by a potential matrix impairs its performance, although this observation is at variance with some other reports. For example, sinapinic acid, with an IR absorption maximum close to the 2.94 µm wavelength of the Er-YAG laser, has been little used as an IR-MALDI matrix. By contrast, succinic acid, with much lower IR absorption and no history of use in UV-MALDI as it has no UV absorption at the wavelength of common UV lasers, has become widely recognized as a good general purpose matrix for IR-MALDI. Despite reports by others that glycerol is an effective matrix for IR-MALDI, we find that glycerol, which also absorbs strongly at 2.94 µm, is useful only if applied as a very thin film. Thus the cumulative evidence for the role of the matrix in IR-MALDI appears confusing and often contradictory. Water has been postulated to be a major contributor to the absorption of energy in IR-MALDI. Consistent with this, we find that samples dried from D2O, which does not absorb at 2.94 µm, give spectra of inferior quality compared with the same samples from H2O. Similarly, samples dried under vacuum, that probably contain less water than those dried in the open laboratory, give weaker and more erratic spectra. Another potential participant in energy absorption and energy transfer is the surface of the metal support, an alternative mechanism for IR-MALDI, for which some evidence is presented here. Copyright © 1999 John Wiley & Sons, Ltd.

The purpose of this investigation was to determine the effects of moderate intensity exercise training during peripuberty on nitrosomethylurea (NMU) induced mammary tumorigenesis and to assess the effects of this activity on mammary epithelial cell proliferation and mammary gland development in rats. Female Sprague Dawley rats were divided into two groups, sedentary and exercised. The rats were exercised five times per week from 21 to 50 days of age on a progressive treadmill training program with a final workload of 18 m/min at 15% incline for 60 min a day. At fifty days of age eight rats from each group were sacrificed to determine the effects of exercise on mammary gland labelling index and development scores. The remaining animals were given NMU at a concentration of 50 mg/kg body weight. The experiment was terminated 24 weeks post carcinogen administration, and cancer incidence, multiplicity, and latency were analyzed. The total tumor number per group was reduced by exercise (58 vs. 33 carcinomas p < 0.05). This corresponded to a significantly higher number of tumors/animal in the sedentary rats compared to those that were exercised prior to NMU administration. However latency period (124.9 ± 4.3 vs. 125.2 ± 6.4) and final incidence (68.9% vs. 61.5%) were not significantly different in sedentary vs. exercised rats. There were no significant differences in mammary gland developmental scores (4.1 ± 0.24 vs. 4.4 ± 0.26) or labelling index of mammary epithelial cells in either ducts or lobuloalveolar units (ductal 41.5 ± 4.7 vs. 39.4 ± 5.7; lobuloalveolar 38.5 ± 4.1 vs. 47.7 ± 5.7) between the two groups. The results of this study suggest that although exercise prior to carcinogen administration has an effect on mammary tumorigenesis, these effects do not appear to be related to exercise-induced changes in mammary gland development.

The analytical utility of matrix-assisted laser desorption ionization (MALDI) mass spectrometry for the characterization of structurally complex polymers is demonstrated. The advantages and limitations of the MALDI method are discussed through the analysis of several low molecular weight copolymers. Oligomer resolution is achieved by using a MALDI time-of-flight mass spectrometer equipped with pulsed ion extraction for time-lag focusing. Accurate mass analysis of the oligomers provides data sufficient for the confirmation of the repeat unit and end group structures for alternating copolymers. It is shown that for alternating copolymers poly[(o-cresyl glycidyl ether)-co-formaldehyde] and glycidyl end-capped poly[(bisphenol A)-co-epichlorohydrin], the molecular weight as well as detailed structural and compositional information can be obtained from a single spectrum of each. It is found to be more difficult to obtain compositional information on block copolymers or random copolymers. Through the analysis of poly[(propylene glycol)-b-(ethylene glycol)-b-(propylene glycol)]bis(2-aminopropyl ether) and Dow polyol A and polyol B, it is shown that prior knowledge of the end group and monomer masses is required to determine information on the monomer composition. Loss of unit mass resolution complicates the analysis for monomer composition. The issue of obtaining the necessary quantitative information for complete characterization of the above polymer systems is also addressed.

We report the synthesis and characterization of a series of poly(ethylene oxide) [PEO] polymers in which two pyrene groups are separated by a common EO87 chain, and flanked by tails of varying EOx length. These polymers were prepared by reacting HO−EO87−OH (Mn = 3841, Mw/Mn = 1.01) with four different N,N-diisopropylphosphoramidites containing both pyrene (Py) and MeO−EOx− substituents. In this way, polymers of the form EOx−Py−EO87−Py−EOx (with MeO end groups) were obtained, with x = 2, 12, 17, and 47. These polymers are particularly useful for studying cyclization kinetics via pyrene excimer formation for two points labeled by pyrenes within the interior of a polymer chain. The polymers were characterized by NMR, size exclusion chromatography, and matrix-assisted laser desorption (MALDI) mass spectroscopy. The MALDI results were particularly informative since each of the oligomers of each of the components could be identified in each mass spectrum.

Antibodies are important tools to explore receptor–ligand interactions. The anti-integrin antibody OPG2 binds in an RGD-related manner to the αIIbβ3integrin as a molecular mimic of fibrinogen. The Fab fragment from OPG2 was cocrystallized with a peptide from the β3subunit of the integrin representing a site that binds RGD. The crystal structure of the complex was determined at 2.2-Å resolution and compared with the unbound Fab. On binding the integrin peptide there were conformational changes in CDR3 of the heavy chain. Also, a significant shift across the intermolecular interface between the CH1-CLdomains was observed so that the angle of rotation relating the two domains was reduced by 15°. This unusual conformational adjustment represents the first example of ligand-induced conformational changes in the carboxyl domains of a Fab fragment.

A data acquisition scheme based on a general-purpose interface bus (GPIB) for data transfer from a digital storage oscilloscope (DSO) to a PC is investigated for recording and storing transient signals generated by laser-induced multiphoton ionization or laser desorption ionization time-of-flight mass spectrometry. With this scheme and the use of commercial software, the data acquisition rate is generally low, typically 1 or 2 Hz for 20-Kbyte transients. We have developed a software to maximize the speed of data transfer and storage. This software is incorporated into LabWindows for data analysis. We demonstrate that it is possible to record and store mass spectra at a speed ranging from 14 spectra/s for a transient record length of 20 Kbytes to 50 spectra/s for a record length of 1 Kbyte by using this DSO-GPIB-PC scheme. This simple and readily adaptable system is found to be adequate and useful for many operations in laser work where relatively higher repetition rates are required. The applications of the system are demonstrated for recording and constructing ion chromatograms in liquid chromatography/time-of-flight mass spectrometry. In addition, it is shown that the data system can not only replace the traditional boxcar integrator for signal monitoring but also provide multiple ion monitoring for recording wavelength spectra in laser ionization spectroscopy.

Continuum spectra from the reaction197Au(p, p') at incident energies of 100, 120, 150, 175 and 200 MeV have been measured at scattering angles from 15° to 120°. The angular distributions at representative ejectile energies are compared with a phenomenological parametrization. Reasonable agreement between calculations and experimental data is obtained, but the comparison clearly indicates a need for modification to the parametrization to incorporate a smooth rather than a sharp transition in the energy dependence over the range investigated. This is physically more realistic and is therefore to be expected. The parametrization facilitates the identification of a contribution which behaves in accordance with a quasifree reaction mechanism. The magnitude and angular extent of the quasifree contribution are much larger than that inferred from earlier experiments.

The elastic scattering of a-particles from28Si at incident energies between 5 and 12 MeV (4.4 and 10.5 MeV in the centre-of-mass system) was studied to ascertain whether quasimolecular states exist for the a+28Si system, as predicted in the literature in terms of a microscopic theory based on the generator coordinate method. Angular distributions were obtained for angles larger than 70°, in energy steps of 100 keV. Analysis of the experimental data was performed by coherently adding specific resonances to an underlying optical model which describes the background portion of the direct elastic scattering amplitude. As is usual, it was furthermore assumed that the average compound elastic contribution adds incoherently to the total cross section. In spite of the presence of a resonance characterized by an angular momentum value ofJ=3 in the energy region, as required by theory, no evidence could be found for the existence of other resonances with the expectedJ-sequence. We conclude that our experiment and analysis do not support the predictions of the microscopic theory.

This article examines the nature and course of panic disorder as understood from a cognitive-behavioral perspective. A model of the causes and maintenance of panic disorder is presented, and is followed by a discussion of the elements and efficacy of cognitive-behavioral treatment. Treatment effects and factors associated with relapse are considered within the context of evidence for a differential course of panic disorder for patients treated with cognitive-behavioral therapy relative to those treated with pharmacotherapy. Issues of combined treatment, maintenance of treatment gains, and preventive interventions are discussed.

Previously we have shown that exercising rats prior to administration of 50 mg NMU/kg (high dose) significantly decreased tumor multiplicity, but not incidence or latency. We hypothesized that the dose of NMU saturated the system such that the exercise intervention was overshadowed. Therefore, the purpose of this investigation was to determine if exercise would have a more pronounced effect with a moderate dose of 37.5 mg NMU/kg. Female Sprague Dawley rats were divided into sedentary and exercised groups. The rats were exercised five times per week from 21 to 50 days of age on a progressive treadmill training program with a final workload of 18 m/min at 15% incline for 60 min a day. At 50 days of age all rats were given an i.p. injection of NMU at 37.5 mg/kg body weight. The experiment was terminated 22 weeks post carcinogen administration. Although there was no difference in terms of tumor incidence, multiplicity, or latency between the two groups, the tumor growth rate (0.107 ± 0.025 vs. 0.043 ± 0.009 g/day) and final tumor weight (3.2 ± 0.74 vs. 1.2 ± 0.34 grams) were significantly higher in the exercised animals. IGF-I receptor (9.4 ± 96 vs. 10.5 ± 57 per µg protein) and estrogen receptor (18.4 ± 1.14 vs. 19.6 ± 1.6 per µg protein) levels were not significantly different in tumors from exercised animals compared to those from sedentary animals. For both sets of tumors, correlation between estrogen receptor content and growth rate is positive, while the correlation between IGF-I receptor content and growth rate is negative. The results of this study suggest that exercise prior to NMU administration does not affect tumor burden but does alter tumor growth rate, which is not due to differences in estrogen receptor or IGF-I receptor content.

An introduction is presented in which the editor discusses various reports within the issue on topics including effects of health care spends on Gross Domestic Product (GDP) of U.S., challenges faced by the health care industry, and health care consumers' choices.

Several letters to the editor are presented in response to articles in previous issues including a letter on the societal and political role of doctors in the September 22, 2006 issue, "More security fears hit Choice system," in the September 29, 2006 issue, and a letter on the lack of physiotherapists in Great Britain.

Presents several letters to the editor about articles appearing in previous issues of "Time."

Reviews the classical music recording of compositions by Witold Lutoslawski and Karol Szymanowski, performed by the Bamberg Symphony Orchestra, under conductor James Judd with Ewa Kupiec on pianoforte. Performance of the Lutoslawski concerto; Comparison of both compositions.