Kallikrein-related peptidases in prostate cancer: From molecular function to clinical application

Prostate cancer is a leading contributor to male cancer-related deaths worldwide. Kallikrein-related peptidases (KLKs) are serine proteases that exhibit deregulated expression in prostate cancer, with KLK3, or prostate specific antigen (PSA), being the widely-employed clinical biomarker for prostate cancer. Other KLKs, such as KLK2, show promise as prostate cancer biomarkers and, additionally, their altered expression has been utilised for the design of KLK-targeted therapies. There is also a large body of in vitro and in vivo evidence supporting their role in cancer-related processes. Here, we review the literature on studies to date investigating the potential of other KLKs, in addition to PSA, as biomarkers and in therapeutic options, as well as their current known functional roles in cancer progression. Increased knowledge of these KLK-mediated functions, including degradation of the extracellular matrix, local invasion, cancer cell proliferation, interactions with fibroblasts, angiogenesis, migration, bone metastasis and tumour growth in vivo, may help define new roles as prognostic biomarkers and novel therapeutic targets for this cancer.

Effects of the sensorimotor training volume on sensorimotor function in patients following lower limb arthroplasty

Background Sensorimotor function is degraded in patients after lower limb arthroplasty. Sensorimotor training is thought to improve sensorimotor skills, however, the optimal training stimulus with regard to volume, frequency, duration, and intensity is still unknown. The aim of this study, therefore, was to firstly quantify the progression of sensorimotor function after total hip (THA) or knee (TKA) arthroplasty and, as second step, to evaluate effects of different sensorimotor training volumes. Methods 58 in-patients during their rehabilitation after THA or TKA participated in this prospective cohort study. Sensorimotor function was assessed using a test battery including measures of stabilization capacity, static balance, proprioception, and gait, along with a self-reported pain and function. All participants were randomly assigned to one of three intervention groups performing sensorimotor training two, four, or six times per week. Outcome measures were taken at three instances, at baseline (pre), after 1.5 weeks (mid) and at the conclusion of the 3 week program (post). Results All measurements showed significant improvements over time, with the exception of proprioception and static balance during quiet bipedal stance which showed no significant main effects for time or intervention. There was no significant effect of sensorimotor training volume on any of the outcome measures. Conclusion We were able to quantify improvements in measures of dynamic, but not static, sensorimotor function during the initial three weeks of rehabilitation following TKA/THA. Although sensorimotor improvements were independent of the training volume applied in the current study, long-term effects of sensorimotor training volume need to be investigated to optimize training stimulus recommendations.

Two-dimensional solidification in a cylindrical mold with imperfect mold contact

A two-dimensional axisymmetric problem of solidification of a superheated liquid in a long cylindrical mold has been studied in this paper by employing a new embedding technique. The mold and the melt has an imperfect contact and the heat transfer coefficient has been taken as a function of space and time. Short-time exact analytical solutions for the moving boundary and temperature distributions in the liquid, solid and mold have been obtained. The numerical results indicate that with the present solution, for some parameter values, substantial solidified thickness can be obtained. The method of solution is simple and straightforward, and consists of assuming fictitious initial temperatures for some suitable fictitious extensions of the actual regions. Sufficient conditions for the commencement of the solidification have been discussed.

A unified approach to the gauging of space-time and internal symmetries

The properties of the manifold of a Lie groupG, fibered by the cosets of a sub-groupH, are exploited to obtain a geometrical description of gauge theories in space-timeG/H. Gauge potentials and matter fields are pullbacks of equivariant fields onG. Our concept of a connection is more restricted than that in the similar scheme of Ne'eman and Regge, so that its degrees of freedom are just those of a set of gauge potentials forG, onG/H, with no redundant components. The ldquotranslationalrdquo gauge potentials give rise in a natural way to a nonsingular tetrad onG/H. The underlying groupG to be gauged is the groupG of left translations on the manifoldG and is associated with a ldquotrivialrdquo connection, namely the Maurer-Cartan form. Gauge transformations are all those diffeomorphisms onG that preserve the fiber-bundle structure.

A Combination of Hexagonal and 12-Sided Polygonal Voltage Space Vector PWM Control for IM Drives Using Cascaded Two-Level Inverters

This paper proposes a multilevel inverter configuration which produces a hexagonal voltage space vector structure in the lower modulation region and a 12-sided polygonal space vector structure in the overmodulation region. A conventional multilevel inverter produces 6n plusmn 1 (n = odd) harmonics in the phase voltage during overmodulation and in the extreme square-wave mode of operation. However, this inverter produces a 12-sided polygonal space vector location, leading to the elimination of 6n plusmn 1 (n = odd) harmonics in the overmodulation region extending to a final 12-step mode of operation with a smooth transition. The benefits of this arrangement are lower losses and reduced torque pulsation in an induction motor drive fed from this converter at higher modulation indexes. The inverter is fabricated by using three conventional cascaded two-level inverters with asymmetric dc-bus voltages. A comparative simulation study of the harmonic distortion in the phase voltage and associated losses in conventional multilevel inverters and that of the proposed inverter is presented in this paper. Experimental validation on a prototype shows that the proposed converter is suitable for high-power applications because of low harmonic distortion and low losses.

Space in Musical Semiosis : An Abductive Theory of the Musical Composition Process

Space in musical semiosis is a study of musical meaning, spatiality and composition. Earlier studies on musical composition have not adequately treated the problems of musical signification. Here, composition is considered an epitomic process of musical signification. Hence the core problems of composition theory are core problems of musical semiotics. The study employs a framework of naturalist pragmatism, based on C. S. Peirce’s philosophy. It operates on concepts such as subject, experience, mind and inquiry, and incorporates relevant ideas of Aristotle, Peirce and John Dewey into a synthetic view of esthetic, practic, and semiotic for the benefit of grasping musical signification process as a case of semiosis in general. Based on expert accounts, music is depicted as real, communicative, representational, useful, embodied and non-arbitrary. These describe how music and the musical composition process are mental processes. Peirce’s theories are combined with current morphological theories of cognition into a view of mind, in which space is central. This requires an analysis of space, and the acceptance of a relativist understanding of spatiality. This approach to signification suggests that mental processes are spatially embodied, by virtue of hard facts of the world, literal representations of objects, as well as primary and complex metaphors each sharing identities of spatial structures. Consequently, music and the musical composition process are spatially embodied. Composing music appears as a process of constructing metaphors—as a praxis of shaping and reshaping features of sound, representable from simple quality dimensions to complex domains. In principle, any conceptual space, metaphorical or literal, may set off and steer elaboration, depending on the practical bearings on the habits of feeling, thinking and action, induced in musical communication. In this sense, it is evident that music helps us to reorganize our habits of feeling, thinking, and action. These habits, in turn, constitute our existence. The combination of Peirce and morphological approaches to cognition serves well for understanding musical and general signification. It appears both possible and worthwhile to address a variety of issues central to musicological inquiry in the framework of naturalist pragmatism. The study may also contribute to the development of Peircean semiotics.

Molecular tools for studying puberty in the grey mullet, Mugil cephalus: cloning of cDNAs that regulate reproductive function

The cDNAs coding for the brain GnRHs (AY373449-51), pituitary GH, SL and PRL, and liver IGFs (AY427954-5) were isolated. Partial cDNA sequences of the brain (Cyp19b) and gonadal (Cyp19a) aromatases have also been obtained. These tools would be utilized to study the endocrine regulation of puberty in the grey mullet.

Systematic Construction of Linear Transform Based Full-Diversity, Rate-One Space-Time Frequency Codes

In this paper, we generalize the existing rate-one space frequency (SF) and space-time frequency (STF) code constructions. The objective of this exercise is to provide a systematic design of full-diversity STF codes with high coding gain. Under this generalization, STF codes are formulated as linear transformations of data. Conditions on these linear transforms are then derived so that the resulting STF codes achieve full diversity and high coding gain with a moderate decoding complexity. Many of these conditions involve channel parameters like delay profile (DP) and temporal correlation. When these quantities are not available at the transmitter, design of codes that exploit full diversity on channels with arbitrary DIP and temporal correlation is considered. Complete characterization of a class of such robust codes is provided and their bit error rate (BER) performance is evaluated. On the other hand, when channel DIP and temporal correlation are available at the transmitter, linear transforms are optimized to maximize the coding gain of full-diversity STF codes. BER performance of such optimized codes is shown to be better than those of existing codes.

A Multilevel Inverter with Hexagonal and 12-sided Polygonal Space Vector Structure for Induction Motor Drive

This paper proposes a multilevel inverter which produces hexagonal voltage space vector structure in lower modulation region and a 12-sided polygonal space vector structure in the over-modulation region. Normal conventional multilevel inverter produces 6n +/- 1 (n=odd) harmonics in the phase voltage during over-modulation and in the extreme square wave mode operation. However, this inverter produces a 12-sided polygonal space vector location leading to the elimination of 6n 1 (n=odd) harmonics in over-modulation region extending to a final 12-step mode operation. The inverter consists of three conventional cascaded two level inverters with asymmetric dc bus voltages. The switching frequency of individual inverters is kept low throughout the modulation index. In the low speed region, hexagonal space phasor based PWM scheme and in the higher modulation region, 12-sided polygonal voltage space vector structure is used. Experimental results presented in this paper shows that the proposed converter is suitable for high power applications because of low harmonic distortion and low switching losses.

Tree species diversity and ecosystem function: Can tropical multi-species plantations generate greater productivity?

Results from the humid tropics of Australia demonstrate that diverse plantations can achieve greater productivity than monocultures. We found that increases in both the observed species number and the effective species richness were significantly related to increased levels of productivity as measured by stand basal area or mean individual tree basal area. Four of five plantation species were more productive in mixtures with other species than in monocultures, offering on average, a 55% increase in mean tree basal area. A general linear model suggests that species richness had a significant effect on mean individual tree basal area when environmental variables were included in the model. As monoculture plantations are currently the preferred reforestation method throughout the tropics these results suggest that significant productivity and ecological gains could be made if multi-species plantations are more broadly pursued.

The effects of holding space on growth and survival of individually reared three-spot crab (Portunus sanguinolentus).

The problem of cannibalism in communally reared crabs can be eliminated by separating the growing crabs into holding compartments. There is currently no information on optimal compartment size for growing crabs individually. 136 second instar crablets (Portunus sanguinolentus) (C2 ca. 7-10 mm carapace width (CW)) were grown for 90 days in 10 different-sized opaque and transparent walled acrylic compartments. The base area for each compartment ranged from small (32 mm × 32 mm) to large (176 mm × 176 mm). Effects of holding space and wall transparency on survival, CW, moult increment, intermoult period and average weekly gain (AWG) were examined. Most crabs reached instars C9-C10 (50-70 mm CW) by the end of experiment. The final survival rate in the smallest compartment was 25% mainly due to moult-related mortality predominantly occurring at the C9 instar. However, crabs in these smaller compartments had earlier produced significantly larger moult increments from instar to instar than those in the larger compartments (P < 0.05). Crabs in the smaller compartments (<65 mm × 65 mm) also showed significantly longer moult periods (P < 0.05). The net result was that AWG in CW was 5.22 mm week-1 for the largest compartment and 5.15 mm week-1 in smallest and did not differ significantly between compartment size groups (P = 0.916). Wall transparency had no impact on survival (P = 0.530) but a slight impact on AWG (P = 0.014). Survival rate was the best indicator of minimum acceptable compartment size (?43 mm × 43 mm) for C10 crablets because below this size death occurred before growth rate was significantly affected. For further growth, it would be necessary to transfer the crablets to larger compartments.

The impact of private and shared open space on liveability in subtropical apartment buildings

The study explores the relationship between open space design, factors impacting open space provision, and resident satisfaction with open space in multistorey apartment buildings in the context of the subtropical lifestyle and climate of Brisbane Australia. The purpose of the paper is to identify the specific physical and spatial design characteristics residents perceive to be important in open spaces associated with their private dwellings and with shared open spaces. Firsthand resident evaluations of everyday experiences of residing in inner urban high density environments are explored through a survey of 636 residents and interviews with 24 residents. Private balconies are highly valued, but residents’ satisfaction would be enhanced by spaciousness for diverse activities, privacy and climate responsive design. Communal spaces and facilities are used infrequently by many residents who prefer interactions with community outside of the building. This is related to preferences for a level of anonymity in a setting where privacy is difficult to achieve due to physical proximity of neighbours.

Serum immunoreactive pancreatic lipase and cationic trypsinogen for the assessment of exocrine pancreatic function in older patients with cystic fibrosis

Indirect and qualitative tests of pancreatic function are commonly used to screen patients with cystic fibrosis for pancreatic insufficiency. In an attempt to develop a more quantitative assessment, we compared the usefulness of measuring serum pancreatic lipase using a newly developed enzyme-linked immunosorbent immunoassay with that of cationic trypsinogen using a radioimmunoassay in the assessment of exocrine pancreatic function in patients with cystic fibrosis. Previously, we have shown neither lipase nor trypsinogen to be of use in assessing pancreatic function prior to 5 years of age because the majority of patients with cystic fibrosis in early infancy have elevated serum levels regardless of pancreatic function. Therefore, we studied 77 patients with cystic fibrosis older than 5 years of age, 41 with steatorrhea and 36 without steatorrhea. In addition, 28 of 77 patients consented to undergo a quantitative pancreatic stimulation test. There was a significant difference between the steatorrheic and nonsteatorrheic patients with the steatorrheic group having lower lipase and trypsinogen values than the nonsteatorrheic group (P < .001). Sensitivities and specificities in detecting steatorrhea were 95% and 86%, respectively, for lipase and 93% and 92%, respectively, for trypsinogen. No correlations were found between the serum levels of lipase and trypsinogen and their respective duodenal concentrations because of abnormally high serum levels of both enzymes found in some nonsteatorrheic patients. We conclude from this study that both serum lipase and trypsinogen levels accurately detect steatorrhea in patients with cystic fibrosis who are older than 5 years but are imprecise indicators of specific pancreatic exocrine function above the level needed for normal fat absorption.

Impaired physical function associated with childhood obesity: How should we intervene?

- Background This study examined relationships between adiposity, physical functioning and physical activity. - Methods Obese (N=107) and healthy-weight (N=132) children aged 10-13 years underwent assessments of percent body fat (%BF, dual energy X-ray absorptiometry), knee extensor strength (KE, isokinetic dynamometry), cardiorespiratory fitness (CRF, peak oxygen uptake by cycle ergometry), physical health-related quality of life (HRQOL), worst pain intensity and walking capacity [six-minute walk (6MWT)]. Structural equation modelling was used to assess relationships between variables. - Results Moderate relationships were observed between %BF and 6MWT, KE strength corrected for mass and CRF relative to mass (r -.36 to -.69, P≤.007). Weak relationships were found between: %BF and physical HRQOL (r -.27, P=.008); CRF relative to mass and physical HRQOL (r -.24, P=.003); physical activity and 6MWT (r .17, P=.004). Squared multiple correlations showed that 29.6% variance in physical HRQOL was explained by %BF, pain and CRF relative to mass, while 28% variance in 6MWT was explained by %BF and physical activity. - Conclusions It appears that children with a higher body fat percentage have poorer KE strength, CRF and overall physical functioning. Reducing percent fat appears to be the best target to improve functioning. However, a combined approach to intervention, targeting reductions in body fat percentage, pain and improvements in physical activity and CRF may assist physical functioning.

Oireista puhuminen lääkärin vastaanotolla : Keskustelunanalyyttinen tutkimus lääkärin kysymyksistä

Talking about symptoms during medical consultation. A conversation analytical study of doctors questions This linguistically oriented conversation analytic study investigates doctors questions and patients answers during medical consultation. The focus is on 1) the syntactic constructions of the doctors questions concerning the patients symptoms, 2) the function of different types of syntactic constructions, and 3) the sequential placement of the questions. The data used in the study consist of 57 videotaped doctor patient encounters in Finnish primary health care. The study shows that the traditional division between open and closed questions is vague and needs to be examined further. Open wh-questions and closed yes/no questions form heterogeneous classes: some of the closed questions can be treated as open and vice versa. Wh-questions which occur during the physical examination are often constructed to elicit short answers. These questions can consist of one word (e.g. milloin when ) which does not move to a new topic but supports the unfinished activity of palpation. During the verbal examination, wh-questions are formulated to elicit long descriptions as answers. For example, by asking mites + X ( what about + X), the doctor can open up a new topic and simultaneously give the patient the opportunity to discuss the topic from his/her perspective. Almost half of the yes/no questions project longer than just a minimal answer (e.g. a short confirmation or rejection). In these questions, the doctors use verbal elements which show that more than just a minimal answer is required. They can, for example, add an indefinite element (joku some or mitään any ) to a yes/no question, add a conjunctive vai ( or ) to the end of the question and thus open a space for various types of answers, or add a suggested answer to the question. In addition, the results show that declarative questions not only check understanding, but display the doctor s diagnosing process, check whether the doctor can move on to the next topic or action, and display implicitly the doctor s idea of what is connected and what is relevant. One aim of the study is to describe how different syntactic structures work together. A typical question chain consists of two or three questions. The first question is an open wh-question that elicits a new topic and creates different types of presuppositions. Contingent questions are constructed as yes/no questions that seek an affirmative answer or as declarative sentences that seek confirmation. Contingent questions can function as repair initiators and thus support achieving mutual understanding. Therefore, they are tools for the doctor to construct a description of the medical problem collaboratively with the patient. The results add to the results of previous studies on questions in medical consultation, but also suggest some corrections. They provide additional evidence for the idea that different types of syntactic constructions are useful in different types of settings. However, they also show that the variety of questions that doctors use is more manifold and diverse than the variety introduced in earlier studies and textbooks.