Bergeenden vinden Slijkgarnaaltjes en rust op nieuwe ruiplaats bij Harlingen

Bergeenden kennen we in Nederland vooral als broedvogel en overwinteraar. ’s Zomers trekken ze langs de kust richting Duitse wadden waar ze hun verenpak vernieuwen. Sinds enkele jaren verblijven Bergeenden in steeds grotere aantallen in de Nederlandse Waddenzee om te ruien. Dieetonderzoek laat zien dat dit waarschijnlijk te maken heeft met de spectaculaire toename van een favoriete voedselbron.

Long term structural dynamics of mechanical systems with local nonlinearities

This paper deals with the long term behavior of periodically excited mechanical systems consisting of linear components and local nonlinearities. The number of degrees of freedom of the linear components is reduced by applying a component mode synthesis technique. Lyapunov exponents are used to identify the character of the long term behavior of a nonlinear dynamic system, which may be periodic, quasi-periodic or chaotic. Periodic solutions are calculated efficiently by solving a two-point boundary value problem using finite differences. Floquet multipliers are calculated to determine the local stability of these solutions and to identify local bifurcation points. The methods presented are applied to a beam system supported by a one-sided linear spring, which reveals very rich, complex dynamic behavior. [Author abstract; 17 Refs; In English

Finite element techniques for nonlinear engineering dynamics

In this paper it is shown how the Finite element technique can be integrated with numerical tools for analysis of nonlinear dynamical systems to obtain a tool for efficient dynamic analysis of multi-degree-of-freedom mechanical systems with local nonlinearities. The developed methodology is applied to a beam system with nonlinear support, representative for this class of systems

Superior activity of fusion protein scFvRit:sFasL over cotreatment with rituximab and Fas agonists

The clinical efficacy of the CD20-specific chimeric monoclonal antibody rituximab is significantly hampered by intrinsic or acquired resistance to therapy. Rituximab activates antibody-dependent cellular cytotoxicity/complement-dependent cytotoxicity-dependent lysis but also induces apoptosis by cross-linking of its target antigen CD20. Recent reports indicate that this apoptotic activity of rituximab can be synergized by cotreatment with Fas agonists. Here, we report on a strategy designed to exploit and optimize the synergy between rituximab and Fas signaling by genetically fusing a rituximab-derived antibody fragment to soluble Fas ligand (sFaSL). The resultant fusion protein, designated scFvRit:sFasL, potently induced CD20-restricted apoptosis in a panel of malignant B-cell lines (10 of 11) and primary patient-derived malignant B cells (two of two non-Hodgkin lymphoma and five of six B cell chronic lymphocytic leukemia). ScFvRit:sFasL efficiently activated CD20 and Fas apoptotic signaling, resulting in a far superior proapoptotic activity compared with cotreatment with rituximab and Fas agonists. ScFvRit:sFasL lacked activity toward normal human B cells and also lacked systemic toxicity in nude mice with no elevation of aspartate aminotransferase and alanine aminotransferase levels or liver caspase-3 activity. In conclusion, scFvRit:sFasL efficiently activates CD20 and Fas-apoptotic signaling and may be useful for the elimination of malignant B cells

Selective induction of apoptosis in leukemic B-lymphoid cells by a CD19-specific TRAIL fusion protein

Although the treatment outcome of lymphoid malignancies has improved in recent years by the introduction of transplantation and antibody-based therapeutics, relapse remains a major problem. Therefore, new therapeutic options are urgently needed. One promising approach is the selective activation of apoptosis in tumor cells by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). This study investigated the pro-apoptotic potential of a novel TRAIL fusion protein designated scFvCD19:sTRAIL, consisting of a CD19-specific single-chain Fv antibody fragment (scFv) fused to the soluble extracellular domain of TRAIL (sTRAIL). Potent apoptosis was induced by scFvCD19:sTRAIL in several CD19-positive tumor cell lines, whereas normal blood cells remained unaffected. In mixed culture experiments, selective binding of scFvCD19:sTRAIL to CD19-positive cells resulted in strong induction of apoptosis in CD19-negative bystander tumor cells. Simultaneous treatment of CD19-positive cell lines with scFvCD19:sTRAIL and valproic acid (VPA) or Cyclosporin A induced strongly synergistic apoptosis. Treatment of patient-derived acute B-lymphoblastic leukemia (B-ALL) and chronic B-lymphocytic leukemia (B-CLL) cells resulted in strong tumoricidal activity that was further enhanced by combination with VPA. In addition, scFvCD19:sTRAIL prevented engraftment of human Nalm-6 cells in xenotransplanted NOD/Scid mice. The pre-clinical data presented here warrant further investigation of scFvCD19:sTRAIL as a potential new therapeutic agent for CD19-positive B-lineage malignancies

Optimization of folic acid, vitamin B-12, and vitamin B-6 supplements in pediatric patients with sickle cell disease

Using homocysteine as a functional marker, we determined optimal folic acid, vitamin B-12, and vitamin B-6 dosages in 21 pediatric sickle cell disease (SCD) patients (11 HbSS, 10 HbSC; 7-16 years). Daily supplements of folic acid (400, 700, or 1,000 mug), vitamin B-12 (1, 3, or 5 U.S. 1989 RDA), and vitamin B-6 (1 or 3 U.S. 1989 RDA) were gradually increased in an 82-week dose-escalation study. Blood was taken at 9 occasions for measurements of erythrocyte (RBC) and serum folate, plasma vitamin B-12, whole-blood vitamin B-6, and plasma homocysteine. Augmentation of folic acid from 700 to 1,000 mug and vitamin B-12 from 3 to 5 RDA did not further decrease homocysteine. Percentages of patients exhibiting significant individual homocysteine decreases amounted to 43% (folic acid from 0 to 400 mug, vitamins B-12 and B-6 from 0 to 1 RDA), 14% (folic acid from 400 to 700 mug), 24% (vitamin B-12 from 1 to 3 RDA), and 18% (vitamin B-6 from 1 to 3 RDA). The lowest plasma homocysteine at 82 weeks was 5.9 +/- 2.2 mumol/L. Patients with HbSS had higher RBC folate than HbSC. The entire group exhibited an inverse relation between RBC folate and hemoglobin. We conclude that RBC folate is less valuable for folate status assessment in SCD patients. Optimal dosages are as follows: 700 mug folic acid (3.5-7 U.S. 1989 RDA), 3 U.S. 1989 RDA vitamin B-12 (4.2-6.0 mug), and 3 U.S. 1989 RDA vitamin B-6 (4.2-6.0 mg). A practical daily combination is 1 mg folic acid (4.3-8.5 U.S. 1998 RDA when taken with meals), 6 mug vitamin B-12 (2.5-5 U.S. 1998 RDA), and 6 mg vitamin B-6 (4.6-10 U.S. 1998 RDA). This combination may by simple and relatively inexpensive means reduce these patients' inherently high risk of endothelial damage