Phase I trial of anti-CD3-stimulated CD4+ T cells, infusional interleukin-2, and cyclophosphamide in patients with advanced cancer

PURPOSE: We performed a phase I trial to determine whether in vivo expansion of activated CD4+ T cells was possible in cancer patients. 111Indium labeling was used to observe trafficking patterns of the infused stimulated CD4+ T cells. The influence of cyclophosphamide (CTX) dosing on immunologic outcome was also examined. PATIENTS AND METHODS: Patients with advanced solid tumors or non-Hodgkin's lymphoma received CTX at 300 or 1,000 mg/m2 intravenously (i.v.). Leukapheresis was performed to harvest peripheral-blood mononuclear cells (PBMCs) either just before the CTX dose, or when the patient was either entering or recovering from the leukocyte nadir induced by CTX. An enriched population of CD4+ T cells was obtained by negative selection. The CD4+ T cells were activated ex vivo with anti-CD3, cultured with interleukin-2 (IL-2) for 4 days, and adoptively transferred. After adoptive transfer, patients received IL-2 (9.0 x 10(6) IU/m2/d) by continuous infusion for 7 days. RESULTS: The absolute number of CD4+, CD4+/DR+, and CD4+/CD45RO+ T cells increased in a statistically significant fashion in all cohorts after the first course of therapy. The degree of CD4 expansion was much greater than CD8 expansion, which resulted in a CD4:CD8 ratio that increased in 26 of 31 patients. The greatest in vivo CD4 expansion occurred when cells were harvested as patients entered the CTX-induced nadir. One complete response (CR), two partial responses (PRs), and eight minor responses were observed. Trafficking of 111Indium-labeled CD4 cells to subcutaneous melanoma deposits was also documented. CONCLUSION: CD4+ T cells can be expanded in vivo in cancer patients, which results in increased CD4:CD8 ratios. The timing of pheresis in relation to CTX administration influences the degree of CD4 expansion. Tumor responses with this regimen were observed in a variety of tumors, including melanoma and non-Hodgkin's lymphoma; a high percentage of patients had at least some tumor regression from the regimen that produced the greatest CD4+ T-cell expansion.     

On the kinetics of isothermal crystallization of branched polyethylene

Isothermal crystallization of branched polyethylene was studied by time-dependent small-angle X-ray scattering experiments and dilatometry. A strict proportionality between scattering intensities and density changes was found for all times. This result indicates complete absence of crystal thickening and perfectioning processes. Isotherms directly reflect the increase in specific inner surface resulting from nucleation and lateral growth of lamellae. The shape of isotherms suggests a time-dependent non-uniform internal structure of spherulites with a decrease in specific inner surface with increasing distance from centre.     

Beschichtungssysteme für Verbindungselemente in Kontakt mit Leichtmetallen

Coating systems for joining elements in contact with light metals Galvanic corrosion of light metal alloys can only be avoided, if the steel fasteners are given an electrochemically compatible protection or if the corrosion circuit is interrupted by electric insulating layers. Current density vs. potential curves of chromated zinc alloy coatings show, that by means of zinc nickel coatings a largely electrochemical adaption to the equilibrium potential of quenchaged aluminium alloys of the type AlMgSi is possible. On the other hand, the equilibrium potentials of chromated systems based on ZnFe, ZnCo respectively, are too low to avoid galvanic corrosion on aluminium. In practicerelated corrosion tests on joining elements, this result was confirmed. Besides this, zinc- and aluminium-bearing sintersystems, galvanic tin depositions as well as ternary mechanical coatings based on ZnSnAl have been proved to be compatible with AlMgSi-type alloys. For coating systems in contact with magnesium a satisfactory protection against galvanic corrosion can be achieved effectively with insulating top coats. The results with suitable duplex systems are presented and recommendations for practical applications are derived.     

Both Epstein-Barr viral nuclear antigen 2 (EBNA2) and activated Notch1 transactivate genes by interacting with the cellular protein RBP-J kappa

The Epstein-Barr viral nuclear antigen 2 (EBNA2) plays a key role during establishment and maintenance of B cell immortalization after Epstein-Barr virus (EBV) infection. EBNA2 acts as a transactivator of cellular and viral genes. We studied two EBNA2 regulated viral promoters (TP1 promoter and LMP/TP2 promoter) in detail to learn more about the molecular mechanisms of EBNA2-mediated transactivation. In both promoters we could identify at least one binding site for the cellular repressor protein RBP-J kappa. EBNA2 is tethered to the EBNA2 responsive promoter elements by interaction with this cellular protein. Although necessary, the binding of RBP-J kappa is not sufficient for EBNA2-mediated transactivation. At least two further cellular proteins, which are different in the studied promoters are important for efficient transactivation. The identification of RBP-J kappa as central mediator of EBNA2 transactivation suggested an interference of EBNA2 with the highly conserved Notch receptor signal transduction pathway. We could show that an activated form of the Notch receptor can transactivate a reporter construct containing a hexamer of the two RBP-J kappa binding sites of the TP1 promoter supporting the idea that EBNA2 acts as a functional equivalent of an activated Notch receptor.     

Raman spectrum of the high pressure phase of polyethylene

Summary The Raman spectrum of the hexagonal high pressure phase of polyethylene was measured at 5.2 kbar and 240 °C, using a hydrostatic high pressure cell. The spectrum is largely identical to that obtained for the melt. This result indicates that the conformational short range order in the hexagonal phase remains melt —like and is not modified by the overall straightening of chains.     

BioRef: a versatile time-of-flight reflectometer for soft matter applications at Helmholtz-Zentrum Berlin

BioRef is a versatile novel time-of-flight reflectometer featuring a sample environment for in situ infrared spectroscopy at the reactor neutron source BER II of the Helmholtz Zentrum Berlin fu?r Materialien und Energie (HZB). After two years of design and construction phase the instrument has recently undergone commissioning and is now available for specular and off-specular neutron reflectivity measurements. BioRef is especially dedicated to the investigation of soft matter systems and studies at the solid-liquid interface. Due to flexible resolution modes and variable addressable wavelength bands that allow for focusing onto a selected scattering vector range, BioRef enables a broad range of surface and interface investigations and even kinetic studies with subsecond time resolution. The instrumental settings can be tailored to the specific requirements of a wide range of applications. The performance is demonstrated by several reference measurements, and the unique option of in situ on-board infrared spectroscopy is illustrated by the example of a phase transition study in a lipid multilayer film.     

Zur Lage des Bergbaus: Entwicklungen auf internationaler und nationaler Ebene

Mineral raw materials are essential for maintaining and improving our quality of life. Thus they are of fundamental importance for a prosperous economy. Global mining production shows an all-time high of 17.4 billion tons in 2014. Asia and Oceania have demonstrated a significant increase in mining production in recent years, whereas Europe shows an opposite trend. In general, the oversupply of mineral raw materials has led to a drop in commodity prices in recent times.     

Induktivitäten in Gleichrichterschaltungen

Zusammenfassung Eine einphasige Drossel mit herausgeführtem Mittelpunkt, die über einen Zweiweggleichrichter in Nullpunktschaltung einen Gleichstromverbraucher speist, kann durch entsprechende Bemessung der Kopplung zwischen ihren beiden Wicklungshälften zur Glättung des Gleichstromes herangezogen werden. Der Aufwand wird dabei zwar größer als bei besonderer Gleichstromdrossel, aber die Aufteilung auf zwei getrennte Einrichtungen, nämlich Transformator und Drossel, wird vermieden. Die Glättung ist mit dem Auftreten eines magnetischen Gleichstromfeldes in der Drossel verknüpft, und die Schaltung ist vorteilhaft verwendbar, wenn nicht der Gleichstrom sondern ein solches Magnetfeld erzeugt werden soll. Außer dem Magneten, der also mit zwei Wicklungen versehen ist und einem Zweiweggleichrichter sind dazu keine weiteren Einrichtungen notwendig. Eine solche Anordnung wurde durch Rechnung und Messung untersucht. Es zeigt sich, daß der Magnet nur um wenige Prozente größer zu bemessen ist, als wenn er mit reinem Gleichstrom erregt wäre und daß das erzeugte Feld nur ganz geringe Oberwellen hat. Der Versuch, bei dem der zeitliche Feldverlauf dadurch bestimmt wurde, daß die vom Feld in einen fremd angetriebenen Kommutatoranker induzierte Ankerspannung gemessen wurde, zeigt weitgehende Übereinstimmung mit der Rechnung.