Hematopoietic progenitor cell content of vertebral body marrow used for combined solid organ and bone marrow transplantation

While cadaveric vertebral bodies (VB) have long been proposed as a suitable source of bone marrow (BM) for transplantation (BMT), they have rarely been used for this purpose. We have infused VB BM immediately following whole organ (WO) transplantation to augment donor cell chimerism. We quantified the hematopoietic progenitor cell (HPC) content of VB BM as well as BM obtained from the iliac crests (IC) of normal allogeneic donors (ALLO) and from patients with malignancy undergoing autologous marrow harvest (AUTO). Patients undergoing WO/BM transplantation also had AUTO BM harvested in the event that subsequent lymphohematopoietic reconstitution was required. Twenty-four VB BM, 24 IC BM-ALLO, 31 IC AUTO, and 24 IC WO-AUTO were harvested. VB BM was tested 12 to 72 hr after procurement and infused after completion of WO grafting. IC BM was tested and then used or cryopreserved immediately. HPC were quantified by clonal assay measuring CFU-GM, BFU-E, and CFU-GEMM, and by flow cytometry for CD34+ progenitor cells. On an average, 9 VB were processed during each harvest, and despite an extended processing time the number of viable nucleated cells obtained was significantly higher than that from IC. Furthermore, by HPC content, VB BM was equivalent to IC BM, which is routinely used for BMT. We conclude that VB BM is a clinically valuable source of BM for allogeneic transplantation. © 1995 by Williams & Wilkins

Parameterized Model-Checking for Timed-Systems with Conjunctive Guards (Extended Version)

In this work we extend the Emerson and Kahlon's cutoff theorems for process skeletons with conjunctive guards to Parameterized Networks of Timed Automata, i.e. systems obtained by an \emph{apriori} unknown number of Timed Automata instantiated from a finite set $U_1, \dots, U_n$ of Timed Automata templates. In this way we aim at giving a tool to universally verify software systems where an unknown number of software components (i.e. processes) interact with continuous time temporal constraints. It is often the case, indeed, that distributed algorithms show an heterogeneous nature, combining dynamic aspects with real-time aspects. In the paper we will also show how to model check a protocol that uses special variables storing identifiers of the participating processes (i.e. PIDs) in Timed Automata with conjunctive guards. This is non-trivial, since solutions to the parameterized verification problem often relies on the processes to be symmetric, i.e. indistinguishable. On the other side, many popular distributed algorithms make use of PIDs and thus cannot directly apply those solutions

de Branges-Rovnyak spaces: basics and theory

For $S$ a contractive analytic operator-valued function on the unit disk ${\mathbb D}$, de Branges and Rovnyak associate a Hilbert space of analytic functions ${\mathcal H}(S)$ and related extension space ${\mathcal D(S)}$ consisting of pairs of analytic functions on the unit disk ${\mathbb D}$. This survey describes three equivalent formulations (the original geometric de Branges-Rovnyak definition, the Toeplitz operator characterization, and the characterization as a reproducing kernel Hilbert space) of the de Branges-Rovnyak space ${\mathcal H}(S)$, as well as its role as the underlying Hilbert space for the modeling of completely non-isometric Hilbert-space contraction operators. Also examined is the extension of these ideas to handle the modeling of the more general class of completely nonunitary contraction operators, where the more general two-component de Branges-Rovnyak model space ${\mathcal D}(S)$ and associated overlapping spaces play key roles. Connections with other function theory problems and applications are also discussed. More recent applications to a variety of subsequent applications are given in a companion survey article

Minimal symmetric Darlington synthesis

We consider the symmetric Darlington synthesis of a p x p rational symmetric Schur function S with the constraint that the extension is of size 2p x 2p. Under the assumption that S is strictly contractive in at least one point of the imaginary axis, we determine the minimal McMillan degree of the extension. In particular, we show that it is generically given by the number of zeros of odd multiplicity of I-SS*. A constructive characterization of all such extensions is provided in terms of a symmetric realization of S and of the outer spectral factor of I-SS*. The authors's motivation for the problem stems from Surface Acoustic Wave filters where physical constraints on the electro-acoustic scattering matrix naturally raise this mathematical issue

Associations between fruit and vegetable intake, leisure-time physical activity, sitting time and self-rated health among older adults : cross-sectional data from the WELL study

BackgroundLifestyle behaviours, such as healthy diet, physical activity and sedentary behaviour, are key elements of healthy ageing and important modifiable risk factors in the prevention of chronic diseases. Little is known about the relationship between these behaviours in older adults. The purpose of this study was to explore the relationship between fruit and vegetable (F&V) intake, leisure-time physical activity (LTPA) and sitting time (ST), and their association with self-rated health in older adults.MethodsThis cross-sectional study comprised 3,644 older adults (48% men) aged 55-65 years, who participated in the Wellbeing, Eating and Exercise for a Long Life ("WELL") study. Respondents completed a postal survey about their health and their eating and physical activity behaviours in 2010 (38% response rate). Spearman\u27s coefficient (rho) was used to evaluate the relationship between F&V intake, LTPA and ST. Their individual and shared associations with self-rated health were examined using ordinal logistic regression models, stratified by sex and adjusted for confounders (BMI, smoking, long-term illness and socio-demographic characteristics).ResultsThe correlations between F&V intake, LTPA and ST were low. F&V intake and LTPA were positively associated with self-rated health. Each additional serving of F&V or MET-hour of LTPA were associated with approximately 10% higher likelihood of reporting health as good or better among women and men. The association between ST and self-rated health was not significant in the multivariate analysis. A significant interaction was found (ST*F&V intake). The effect of F&V intake on self-rated health increased with increasing ST in women, whereas the effect decreased with increasing ST in men.ConclusionThis study contributes to the scarce literature related to lifestyle behaviours and their association with health indicators among older adults. The findings suggest that a modest increase in F&V intake, or LTPA could have a marked effect on the health of older adults. Further research is needed to fully understand the correlates and determinants of lifestyle behaviours, particularly sitting time, in this age group

Epidemics on contact networks: a general stochastic approach

Dynamics on networks is considered from the perspective of Markov stochastic processes. We partially describe the state of the system through network motifs and infer any missing data using the available information. This versatile approach is especially well adapted for modelling spreading processes and/or population dynamics. In particular, the generality of our systematic framework and the fact that its assumptions are explicitly stated suggests that it could be used as a common ground for comparing existing epidemics models too complex for direct comparison, such as agent-based computer simulations. We provide many examples for the special cases of susceptible-infectious-susceptible (SIS) and susceptible-infectious-removed (SIR) dynamics (e.g., epidemics propagation) and we observe multiple situations where accurate results may be obtained at low computational cost. Our perspective reveals a subtle balance between the complex requirements of a realistic model and its basic assumptions.Comment: Main document: 16 pages, 7 figures. Electronic Supplementary Material (included): 6 pages, 1 tabl

Identification and validation of oncologic miRNA biomarkers for Luminal A-like breast cancer

Introduction: Breast cancer is a common disease with distinct tumor subtypes phenotypically characterized by ER and HER2/neu receptor status. MiRNAs play regulatory roles in tumor initiation and progression, and altered miRNA expression has been demonstrated in a variety of cancer states presenting the potential for exploitation as cancer biomarkers. Blood provides an excellent medium for biomarker discovery. This study investigated systemic miRNAs differentially expressed in Luminal A-like (ER+PR+HER2/neu-) breast cancer and their effectiveness as oncologic biomarkers in the clinical setting. Methods: Blood samples were prospectively collected from patients with Luminal A-like breast cancer (n=54) and controls (n=56). RNA was extracted, reverse transcribed and subjected to microarray analysis (n=10 Luminal A-like; n=10 Control). Differentially expressed miRNAs were identified by artificial neural network (ANN) data-mining algorithms. Expression of specific miRNAs was validated by RQ-PCR (n=44 Luminal A; n=46 Control) and potential relationships between circulating miRNA levels and clinicopathological features of breast cancer were investigated. Results: Microarray analysis identified 76 differentially expressed miRNAs. ANN revealed 10 miRNAs for further analysis ( miR-19b, miR-29a, miR-93, miR-181a, miR-182, miR-223, miR-301a, miR-423-5p, miR-486-5 and miR-652 ). The biomarker potential of 4 miRNAs ( miR-29a, miR-181a , miR-223 and miR-652 ) was confirmed by RQ-PCR, with significantly reduced expression in blood of women with Luminal A-like breast tumors compared to healthy controls (p=0.001, 0.004, 0.009 and 0.004 respectively). Binary logistic regression confirmed that combination of 3 of these miRNAs ( miR-29a, miR-181a and miR-652 ) could reliably differentiate between cancers and controls with an AUC of 0.80. Conclusion: This study provides insight into the underlying molecular portrait of Luminal A-like breast cancer subtype. From an initial 76 miRNAs, 4 were validated with altered expression in the blood of women with Luminal A-like breast cancer. The expression profiles of these 3 miRNAs, in combination with mammography, has potential to facilitate accurate subtype- specific breast tumor detection

Micro-Flow Imaging: Flow Microscopy Applied to Sub-visible Particulate Analysis in Protein Formulations

The need to monitor, measure, and control sub-visible proteinaceous particulates in biopharmaceutical formulations has been emphasized in recent publications and commentaries. Some of these particulates can be highly transparent, fragile, and unstable. In addition, for much of the size range of concern, no practical measurement method with adequate sensitivity and repeatability has been available. A complication in measuring protein particulates in many formulations is the simultaneous presence of other particle types such as silicone micro-droplets, air bubbles, and extrinsic contaminants. The need has therefore been identified for new analytical methods which can accurately measure and characterize sub-visible particulates in formulations. Micro-flow imaging has been shown to provide high sensitivity in detecting and imaging transparent protein particles and a unique capability to independently analyze such populations even when other particle types are present

Characterisation and expression of SPLUNC2, the human orthologue of rodent parotid secretory protein

We recently described the Palate Lung Nasal Clone (PLUNC) family of proteins as an extended group of proteins expressed in the upper airways, nose and mouth. Little is known about these proteins, but they are secreted into the airway and nasal lining fluids and saliva where, due to their structural similarity with lipopolysaccharide-binding protein and bactericidal/permeability-increasing protein, they may play a role in the innate immune defence. We now describe the generation and characterisation of novel affinity-purified antibodies to SPLUNC2, and use them to determine the expression of this, the major salivary gland PLUNC. Western blotting showed that the antibodies identified a number of distinct protein bands in saliva, whilst immunohistochemical analysis demonstrated protein expression in serous cells of the major salivary glands and in the ductal lumens as well as in cells of minor mucosal glands. Antibodies directed against distinct epitopes of the protein yielded different staining patterns in both minor and major salivary glands. Using RT-PCR of tissues from the oral cavity, coupled with EST analysis, we showed that the gene undergoes alternative splicing using two 5' non-coding exons, suggesting that the gene is regulated by alternative promoters. Comprehensive RACE analysis using salivary gland RNA as template failed to identify any additional exons. Analysis of saliva showed that SPLUNC2 is subject to N-glycosylation. Thus, our study shows that multiple SPLUNC2 isoforms are found in the oral cavity and suggest that these proteins may be differentially regulated in distinct tissues where they may function in the innate immune response

Serotonin tranporter methylation and response to cognitive behaviour therapy in children with anxiety disorders

Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT