Mixture distribution latent state-trait analysis: Basic ideas and applications.

Extensions of latent state-trait models for continuous observed variables to mixture latent state-trait models with and without covariates of change are presented that can separate individuals differing in their occasion-specific variability. An empirical application to the repeated measurement of mood states (N = 501) revealed that a model with 2 latent classes fits the data well. The larger class (76%) consists of individuals whose mood is highly variable, whose general well-being is comparatively lower, and whose mood variability is influenced by daily hassles and uplifts. The smaller class (24%) represents individuals who are rather stable and happier and whose mood is influenced only by daily uplifts but not by daily hassles. A simulation study on the model without covariates with 5 sets of sample sizes and 5 sets of number of occasions revealed that the appropriateness of the parameter estimates of this model depends on number of observations (the higher the better) and number of occasions (the higher the better). Another simulation study estimated Type I and II errors of the Lo-Mendell-Rubin test. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

3D Radiation Therapy Boost Improves the Outcome of Whole Brain Radiation Therapy Treated RPA II Patients with One or Two Brain Metastases

Purpose

to evaluate the role of whole brain radiotherapy (WBRT) and radiation boost (RB) for 208 patients recursive partitioning analysis (RPA) II with 1 or 2 brain metastases (BM) at a single institution.

Methods and Materials

the dose of WBRT was 30 Gy (10 fractions of 3 Gy). One hundred thirty-two patients (63.5%) benefited from RB of 9 Gy in 3 fractions of 3 Gy at the metastatic site. Patients had 1 or 2 BM in 122 (58.7%) and 86 cases (41.3%), respectively.

Results

patients with one or two metastases had similar survival (4.6 and 5.1 months, respectively) (p = 0.4). Median overall survival (OS) for patients treated with WBRT and RB, and with WBRT alone was 5.9 and 3.7 months, respectively (p = 0.03). The 6-, 12- and 24-month OS rates after WBRT and RB were 48.5%, 25% and 10.6%, respectively, while WBRT alone resulted in OS rates of 34%, 22.4% and 3.2%, respectively (p = 0.03). After WBRT and RB, the 6-, 12- and 24-month local control rates were 92%, 82% and 67%, respectively, while they were 81.2%, 75% and 37.5%, respectively, after WBRT alone (p = 0.03). The 6-, 12- and 24-month brain control rates after WBRT and RB were 88.7%, 75.8% and 62%, respectively, and after WBRT alone they were 78.5%, 59% and 37.7%, respectively (p = 0.03).

Conclusion

additional boost delivered with 3D conformal radiotherapy improves local and brain control rates significantly as well as overall survival for RPA II patients with 1 or 2 unresectable BM.     

LAIR1, an ITIM-Containing Receptor Involved in Immune Disorders and in Hematological Neoplasms

Leukocyte-associated immunoglobulin (Ig)-like receptor 1 (LAIR1, CD305) belongs to the family of immune-inhibitory receptors and is widely expressed on hematopoietic mature cells, particularly on immune cells. Four different types of ligands of LAIR1 have been described, including collagens, suggesting a potential immune-regulatory function on the extracellular matrix. By modulating cytokine secretion and cellular functions, LAIR1 displays distinct patterns of expression among NK cell and T/B lymphocyte subsets during their differentiation and cellular activation and plays a major negative immunoregulatory role. Beyond its implications in physiology, the activity of LAIR1 can be inappropriately involved in various autoimmune or inflammatory disorders and has been implicated in cancer physiopathology, including hematological neoplasms. Its action as an inhibitory receptor can result in the dysregulation of immune cellular responses and in immune escape within the tumor microenvironment. Furthermore, when expressed by tumor cells, LAIR1 can modulate their proliferation or invasion properties, with contradictory pro- or anti-tumoral effects depending on tumor type. In this review, we will focus on its role in normal physiological conditions, as well as during pathological situations, including hematological malignancies. We will also discuss potential therapeutic strategies targeting LAIR1 for the treatment of various autoimmune diseases and cancer settings.     

Postconditioning by Delayed Administration of Ciclosporin A: Implication for Donation after Circulatory Death (DCD)

Heart transplantation is facing a shortage of grafts. Donation after Circulatory Death (DCD) would constitute a new potential of available organs. In the present work, we aimed to evaluate whether Postconditioning (ischemic or with ciclosporin-A (CsA)) could reduce ischemia-reperfusion injury in a cardiac arrest model when applied at the start of reperfusion or after a delay. An isolated rat heart model was used as a model of DCD. Hearts were submitted to a cardiac arrest of 40 min of global warm ischemia (37 °C) followed by 3 h of 4 °C-cold preservation, then 60 min reperfusion. Hearts were randomly allocated into the following groups: control, ischemic postconditioning (POST, consisting of two episodes each of 30 s ischemia and 30 s reperfusion at the onset of reperfusion), and CsA group (CsA was perfused at 250 nM for 10 min at reperfusion). In respective subgroups, POST and CsA were applied after a delay of 3, 10, and 20 min. Necrosis was lower in CsA and POST versus controls (p < 0.01) whereas heart functions were improved (p < 0.01). However, while the POST lost its efficacy if delayed beyond 3 min of reperfusion, CsA treatment surprisingly showed a reduction of necrosis even if applied after a delay of 3 and 10 min of reperfusion (p < 0.01). This cardioprotection by delayed CsA application correlated with better functional recovery and higher mitochondrial respiratory index. Furthermore, calcium overload necessary to induce mitochondrial permeability transition pore (MPTP) opening was similar in all cardioprotection groups, suggesting a crucial role of MPTP in this delayed protection of DCD hearts.     

Development of Anti-LRRC15 Small Fragments for Imaging Purposes Using a Phage-Display ScFv Approach

The human leucine-rich repeat-containing protein 15 (LRRC15) is a membrane protein identified as a marker of CAF (cancer-associated fibroblast) cells whose overexpression is positively correlated with cancer grade and outcome. Nuclear molecular imaging (i.e., SPECT and PET) to track LRRC15 expression could be very useful in guiding further therapeutic strategies. In this study, we developed an ScFv mouse phage-display library to obtain small fragment antibodies against human LRRC15 for molecular imaging purposes. Mice were immunized with recombinant human LRRC15 (hLRRC15), and lymph node cells were harvested for ScFv (single-chain variable fragment) phage-display analysis. The built library was used for panning on cell lines with constitutive or induced expression after transfection. The choice of best candidates was performed by screening various other cell lines, using flow cytometry. The selected candidates were reformatted into Cys-ScFv or Cys-diabody by addition of cysteine, and cloned in mammalian expression vectors to obtain batches of small fragments that were further used in site-specific radiolabeling tests. The obtained library was 1.2 × 10⁷ cfu/µg with an insertion rate >95%. The two panning rounds performed on cells permittedenrichment of 2 × 10⁻³. Screening with flow cytometry allowed us to identify 28 specific hLRRC15 candidates. Among these, two also recognized murine LRCC15 and were reformatted into Cys-ScFv and Cys-diabody. They were expressed transiently in a mammalian system to obtain 1.0 to 4.5 mg of Cys fragments ready for bioconjugation and radiolabeling. Thus, in this paper, we demonstrate the relevance of the phage-display ScFv library approach for the fast-track development of small antibodies for imaging and/or immunotherapy purposes.     

Delay compensated control of the Stefan problem and robustness to delay mismatch

This paper presents a control design for the one‐phase Stefan problem under actuator delay via a backstepping method. The Stefan problem represents a liquid‐solid phase change phenomenon which describes the time evolution of a material's temperature profile and the interface position. The actuator delay is modeled by a first‐order hyperbolic partial differential equation (PDE), resulting in a cascaded transport‐diffusion PDE system defined on a time‐varying spatial domain described by an ordinary differential equation (ODE). Two nonlinear backstepping transformations are utilized for the control design. The setpoint restriction is given to guarantee a physical constraint on the proposed controller for the melting process. This constraint ensures the exponential convergence of the moving interface to a setpoint and the exponential stability of the temperature equilibrium profile and the delayed controller in the norm. Furthermore, robustness analysis with respect to the delay mismatch between the plant and the controller is studied, which provides analogous results to the exact compensation by restricting the control gain.     

Unexpected Interacting Effects of Physical (Radiation) and Chemical (Bisphenol A) Treatments on Male Reproductive Functions in Mice

For decades, numerous chemical pollutants have been described to interfere with endogenous hormone metabolism/signaling altering reproductive functions. Among these endocrine disrupting substances, Bisphenol A (BPA), a widely used compound, is known to negatively impact germ and somatic cells in the testis. Physical agents, such as ionizing radiation, were also described to perturb spermatogenesis. Despite the fact that we are constantly exposed to numerous environmental chemical and physical compounds, very few studies explore the impact of combined exposure to chemical and physical pollutants on reproductive health. The aim of this study was to describe the impact of fetal co-exposure to BPA and IR on testicular function in mice. We exposed pregnant mice to 10 µM BPA (corresponding to 0.5 mg/kg/day) in drinking water from 10.5 dpc until birth, and we irradiated mice with 0.2 Gy (γ-ray, RAD) at 12.5 days post-conception. Co-exposure to BPA and γ-ray induces DNA damage in fetal germ cells in an additive manner, leading to a long-lasting decrease in germ cell abundance. We also observed significant alteration of adult steroidogenesis by RAD exposure independently of the BPA exposure. This is illustrated by the downregulation of steroidogenic genes and the decrease of the number of adult Leydig cells. As a consequence, courtship behavior is modified, and male ultrasonic vocalizations associated with courtship decreased. In conclusion, this study provides evidence for the importance of broadening the concept of endocrine disruptors to include physical agents, leading to a reevaluation of risk management and regulatory decisions.     

Three-Dimensional Cell Culture: A Breakthrough in Vivo

Cell culture is an important tool for biological research. Two-dimensional cell culture has been used for some time now, but growing cells in flat layers on plastic surfaces does not accurately model the in vivo state. As compared to the two-dimensional case, the three-dimensional (3D) cell culture allows biological cells to grow or interact with their surroundings in all three dimensions thanks to an artificial environment. Cells grown in a 3D model have proven to be more physiologically relevant and showed improvements in several studies of biological mechanisms like: cell number monitoring, viability, morphology, proliferation, differentiation, response to stimuli, migration and invasion of tumor cells into surrounding tissues, angiogenesis stimulation and immune system evasion, drug metabolism, gene expression and protein synthesis, general cell function and in vivo relevance. 3D culture models succeed thanks to technological advances, including materials science, cell biology and bioreactor design.     

In‐depth characterization of granular starch‐graft‐polyester compositions as obtained by in situ polymerization of lactones from the starch surface

The synthesis of poly(ε‐caprolactone) (PCL)‐grafted granular starch was carried out either in bulk (without solvent) or in toluene suspension by a two‐step procedure. First step relied upon the activation of the hydroxyl groups available at the starch surface by alkylaluminum derivatives like AlEt₃ and removal of non‐surface‐grafted organo‐aluminum active species. The latter species were made free in solution by reaction with the remaining water molecules still contaminating the polymerization medium despite intensive drying of the starch granules. In the second step, ε‐caprolactone was polymerized via a coordination‐insertion ring‐opening polymerization as initiated by the surface‐grafted aluminum alkoxide species. The present contribution aims at investigating various parameters such as nature of the alkyl aluminum activator and monomer (δ‐valerolactone was studied as well), temperature, concentration, and addition of a solvent (polymerization in toluene suspension), reaction time, and also the experimental procedure used to recover the polyester chains and measure the grafting efficiency. It turns out that, under the studied conditions, dialkylaluminum alkoxides surface‐grafted onto the starch granules were more likely generated and promote a fast polymerization reaction with the formation of grafted PCL chains with a molecular weight that can be as high as 225 000 (M_n value) for polymerization carried out in toluene suspension. Copyright © 2004 Society of Chemical Industry