Biomimetic reconstruction of the hematopoietic stem cell niche for in vitro amplification of human hematopoietic stem cells.

Hematopoietic stem cell transplantation is successfully applied since the late 1950s; however, its efficacy still needs to be increased. A promising strategy is to transplant high numbers of pluripotent hematopoietic stem cells (HSCs). Therefore, an improved ex vivo culture system that supports proliferation and maintains HSC pluripotency would override possible limitations in cell numbers gained from donors. To model the natural HSC niche in vitro, we optimized the HSC medium composition with a panel of cytokines and valproic acid and used an artificial 3D bone marrow-like scaffold made of polydimethylsiloxane (PDMS). This 3D scaffold offered a suitable platform to amplify human HSCs in vitro and, simultaneously, to support their viability, multipotency and ability for self-renewal. Silicon oxide-covering of PDMS structures further improved amplification of CD34+ cells, although the conservation of naïve HSCs was better on non-covered 3D PDMS. Finally, we found that HSC cultivated on non-covered 3D PDMS generated most pluripotent colonies within colony forming unit assays. In conclusion, by combining biological and biotechnological approaches, we optimized in vitro HSCs culture conditions, resulting in improved amplification, multipotency maintenance and vitality of HSCs.

Attosecond spectroscopy in condensed matter.

Comprehensive knowledge of the dynamic behaviour of electrons in condensed-matter systems is pertinent to the development of many modern technologies, such as semiconductor and molecular electronics, optoelectronics, information processing and photovoltaics. Yet it remains challenging to probe electronic processes, many of which take place in the attosecond (1 as = 10(-18) s) regime. In contrast, atomic motion occurs on the femtosecond (1 fs = 10(-15) s) timescale and has been mapped in solids in real time using femtosecond X-ray sources. Here we extend the attosecond techniques previously used to study isolated atoms in the gas phase to observe electron motion in condensed-matter systems and on surfaces in real time. We demonstrate our ability to obtain direct time-domain access to charge dynamics with attosecond resolution by probing photoelectron emission from single-crystal tungsten. Our data reveal a delay of approximately 100 attoseconds between the emission of photoelectrons that originate from localized core states of the metal, and those that are freed from delocalized conduction-band states. These results illustrate that attosecond metrology constitutes a powerful tool for exploring not only gas-phase systems, but also fundamental electronic processes occurring on the attosecond timescale in condensed-matter systems and on surfaces.

Patent foramen ovale is an important predictor of adverse outcome in patients with major pulmonary embolism.

BACKGROUND: Right-to-left shunt through a patent foramen ovale is frequently diagnosed by contrast echocardiography and can be particularly prominent in the presence of elevated pressures in the right side of the heart. Its prognostic significance in patients with pulmonary thromboembolism, however, is unknown. METHODS AND RESULTS: The present prospective study included 139 consecutive patients with major pulmonary embolism diagnosed on the basis of clinical, echocardiographic, and cardiac catheterization criteria. All patients underwent contrast echocardiography at presentation. The end points of the study were overall mortality and complicated clinical course during the hospital stay defined as death, cerebral or peripheral arterial thromboembolism, major bleeding, or need for endotracheal intubation or cardiopulmonary resuscitation. Patent foramen ovale was diagnosed in 48 patients (35%). These patients had a death rate of 33% as opposed to 14% in patients with a negative echo-contrast examination (P=.015). Logistic regression analysis demonstrated that the only independent predictors of mortality in the study population were a patent foramen ovale (odds ratio [OR], 11.4; P<.001) and arterial hypotension at presentation (OR, 26.3; P<.001). Patients with a patent foramen ovale also had a significantly higher incidence of ischemic stroke (13% versus 2.2%; P=.02) and peripheral arterial embolism (15 versus 0%; P<.001). Overall, the risk of a complicated in-hospital course was 5.2 times higher in this patient group (P<.001). CONCLUSIONS: In patients with major pulmonary embolism, echocardiographic detection of a patent foramen ovale signifies a particularly high risk of death and arterial thromboembolic complications.