Facilitated engraftment of human hematopoietic cells in severe combined immunodeficient mice following a single injection of Cl²MDP liposomes

Transplantation of normal and malignant human hematopoietic cells into severe combined immunodeficient (SCID) mice allows for evaluation of long-term growth abilities of these cells and provides a preclinical model for therapeutic interventions. However, large numbers of cells are required for successful engraftment in preirradiated mice due to residual graft resistance, that may be mediated by cells from the mononuclear phagocytic system. Intravenous (i.v.) injection of liposomes containing dichloromethylene diphosphonate (Cl2MDP) may eliminate mouse macrophages in spleen and liver. In this study outgrowth of acute myeloid leukemia (AML) cells and umbilical cord blood (UCB) cells in SCID mice conditioned with a single i.v. injection of Cl2MDP liposomes in addition to sublethal total body irradiation (TBI) was compared to outgrowth of these cells in SCID mice that had received TBI alone. A two- to 10-fold increase in outgrowth of AML cells was observed in four cases of AML. Administration of 107 UCB cells reproducibly engrafted SCID mice that had been conditioned with Cl2MDP liposomes and TBI, whereas human cells were not detected in mice conditioned with TBI alone. As few as 2 x 104 purified CD34+ UCB cells engrafted in all mice treated with Cl2MDP liposomes. In SCID mice treated with macrophage depletion unexpected graft failures were not observed. Histological examination of the spleen showed that TBI and Cl2MDP liposomes i.v. resulted in a transient elimination of all macrophage subsets in the spleen, whereas TBI had a minor effect. Cl2MDP liposomes were easy to use and their application was not associated with appreciable side-effects. Cl2MDP liposome pretreatment in combination with TBI allows for reproducible outgrowth of high numbers of human hematopoietic cells in SCID mice

Теплофизические модели слоисто-неоднородных горных массивов

Стисло розглянуто математичні моделі процесів переносу тепла в шаруватонеоднорідних гірничих масивах. Запропоновано загальний метод моделювання теплопереносу в шаруватих системах різної геометрії. Знайдено рівняння «склеювання», за допомогою якого розглянуто асимптотичні випадки.Mathematical models of heat transfer in layered inhomogeneous rock media are summarized. A general method of modeling the heat transfer in layered systems of a different geometry is proposed. A “matching” equation for different asymptotic cases has been found

A Self-management Approach for Dietary Sodium Restriction in Patients With CKD:A Randomized Controlled Trial

Health and self-regulatio

Phase Transformation for the Large-Scale Synthesis and Assembly via Welding of Metal Silicide Nanowires for Thermoelectric Applications

Solid-state thermoelectrics that convert thermal energy into electricity have the potential to increase the efficiencies of existing process and systems (e.g., automobiles). The large-scale deployment of thermoelectrics for terrestrial use requires the following: a) enhancing their efficiencies beyond that are currently possible, and b) their fabrication from non-toxic, inexpensive, earth-abundant elements. Recent studies have determined that nanostructuring of earth-abundant materials, such as magnesium silicide (Mg2Si), is a possible pathway for accomplishing this task. Contextually, the overall aim of this dissertation is to engineer highly efficient Mg2Si nanowire-based thermoelectrics. This was achieved through the design of strategies for (1) the large-scale synthesis of a form of nanostructured Mg2Si, nanowires of Mg2Si, and (2) the interface-engineered assembly of the synthesized nanowires into welded nanowire networks that do not have any insulating MgO at the nanowire interfaces. Together, these strategies are intended to offer the ability to control thermal and electrical transport through Mg2Si. For the large-scale synthesis of Mg2Si nanowires, a phase transformation strategy that converts pre-synthesized silicon nanowires into Mg2Si nanowires was engineered. Experimentation performed indicated that 20 to 300 nm-thick, 5 to 20 µm-long silicon nanowires obtained by electroless etching can be phase transformed into polycrystalline Mg2Si nanowires by reacting them with magnesium supplied via the vapor phase. To prevent the formation of multiple nuclei within each silicon nanowire during the phase transformation process and the formation of polycrystalline Mg2Si nanowires, a solid-state phase transformation process was engineered. Here, the solid-state reaction of sharp-tipped silicon nanowires with magnesium foils was employed for obtaining single-crystalline Mg2Si nanowires. To assemble the nanowires, the solid-state phase transformation strategy was extended and the phase transformation of silica nanoparticle coated silicon nanowires was employed. This procedure led to the formation of welded Mg2Si nanowire networks, where both the nanowires and the bridges connecting the nanowires were composed of Mg2Si. Thermoelectric performance evaluation of these networks and microcrystalline Mg2Si devices proved our hypothesis and indicated a 2-fold increase in the power factors. The high power factor of 0.972 x 10^-3 Wm^-1K^-2 achieved at 875 K is twice that reported in the literature for undoped Mg2Si

Protective Efficacy of Newcastle Disease Virus Expressing Soluble Trimeric Hemagglutinin against Highly Pathogenic H5N1 Influenza in Chickens and Mice

Background: Highly pathogenic avian influenza virus (HPAIV) causes a highly contagious often fatal disease in poultry, resulting in significant economic losses in the poultry industry. HPAIV H5N1 also poses a major public health threat as it can be transmitted directly from infected poultry to humans. One effective way to combat avian influenza with pandemic potential is through the vaccination of poultry. Several live vaccines based on attenuated Newcastle disease virus (NDV) that express influenza hemagglutinin (HA) have been developed to protect chickens or mammalian species against HPAIV. However, the zoonotic potential of NDV raises safety concerns regarding the use of live NDV recombinants, as the incorporation of a heterologous attachment protein may result in the generation of NDV with altered tropism and/or pathogenicity. Methodology/Principal Findings: In the present study we generated recombinant NDVs expressing either full length, membrane-anchored HA of the H5 subtype (NDV-H5) or a soluble trimeric form thereof (NDV-sH5 3). A single intramuscular immunization with NDV-sH5 3 or NDV-H5 fully protected chickens against disease after a lethal challenge with H5N1 and reduced levels of virus shedding in tracheal and cloacal swabs. NDV-sH5 3 was less protective than NDV-H5 (50% vs 80% protection) when administered via the respiratory tract. The NDV-sH5 3 was ineffective in mice, regardless of whether administered oculonasally or intramuscularly. In this species, NDV-H5 induced protective immunity against HPAIV H5N1, but only after oculonasal administration, despite the poor H5-specific serum antibody response it elicited. Conclusions/Significance: Although NDV expressing membrane anchored H5 in general provided better protection than its counterpart expressing soluble H5, chickens could be fully protected against a lethal challenge with H5N1 by using the latter NDV vector. This study thus provides proof of concept for the use of recombinant vector vaccines expressing a soluble form of a heterologous viral membrane protein. Such vectors may be advantageous as they preclude the incorporation of heterologous membrane proteins into the viral vector particles

Ongecontroleerde verspreiding van cyclophosphamide in ziekenhuizen als bron van beroepsmatige blootstelling

Contains fulltext : 22637___.PDF (publisher's version ) (Open Access

Occupational exposure to antineoplastic agents and parameters for renal dysfunction

Contains fulltext : 24550___.PDF (publisher's version ) (Open Access

Exposure of pharmacy technicians to antineoplastic agents : reevaluation after additional protective measures

Contains fulltext : 25828___.PDF (publisher's version ) (Open Access

Cancer risk assesment for health care workers occupationally exposed to cyclphosphamide

Contains fulltext : 21618___.PDF (publisher's version ) (Open Access