Continuous wave interdigital H-mode cavities for alternating phase focusing heavy ion acceleration.

In the future, a new superconducting (SC) continuous wave (CW) high intensity heavy ion HElmholtz LInear ACcelerator (HELIAC) should provide ion beams with maximum beam energy above the Coulomb barrier for the Super Heavy Element program at GSI (Gesellschaft für Schwerionenforschung, in Engl.: Association for Heavy Ion Research). The HELIAC consists of a SC main accelerator supplied by a normal conducting injector, which comprises an electron cyclotron resonance ion source, a radio-frequency quadrupole, and two separate interdigital H-mode drift-tube linear accelerator cavities, based on an Alternating Phase Focusing (APF) scheme. Together, both cavities will accelerate ions from 300 to 1400 keV/u with only one external quadrupole triplet for transverse focusing in between. Due to the demanding requirements of the APF concept on the voltage distribution along the beam axis on the one hand and the CW operation on the other hand, the optimization of each cavity concerning RF, mechanical, and thermal properties is crucial for the successful operation of the HELIAC injector.

A dynamic collimation and alignment system for the Helmholtz linear accelerator.

The upcoming commissioning of the superconducting (SC) continuous wave Helmholtz linear accelerators first of series cryomodule is going to demand precise alignment of the four internal SC cavities and two SC solenoids. For optimal results, a beam-based alignment method is used to reduce the misalignment of the whole cryomodule, as well as its individual components. A symmetric beam of low transverse emittance is required for this method, which is to be formed by a collimation system. It consists of two separate plates with milled slits, aligned in the horizontal and vertical direction. The collimation system and alignment measurements are proposed, investigated, and realized. The complete setup of this system and its integration into the existing environment at the GSI High Charge State Injector are presented, as well as the results of the recent reference measurements.

Harmonization of BCR-ABL mRNA quantification using a uniform multifunctional control plasmid in 37 international laboratories.

Individualized PCR strategies hamper comparability of molecular results between different laboratories in several fields of medicine. To harmonize BCR-ABL mRNA quantification an international multicenter trial involving 37 laboratories in 14 countries was initiated using 10 samples, each containing various dilutions (10, 2, 1 and 0.1%) of b3a2 or b2a2 BCR-ABL positive in normal leukocytes and negative controls. A novel control plasmid (pME-2) was designed for external calibration containing BCR-ABL and glucuronidase-beta (GUS) sequences. Median BCR-ABL/ABL ratios were 9.1, 1.8, 0.85 and 0.11% in b3a2 samples and 9.5, 1.6, 0.84 and 0.11% in b2a2 samples. Median BCR-ABL/GUS ratios were 3.4, 0.77, 0.37 and 0.042% in b3a2 samples and 2.8, 0.48, 0.29 and 0.031% in b2a2 samples. The coefficients of variation were 0.62 for ratios BCR-ABL/ABL and 1.03 for ratios BCR-ABL/GUS. Five of 37 evaluable participating laboratories (13%) detected low BCR-ABL copy numbers in negative control samples; one laboratory failed to detect BCR-ABL in a low-level sample. We conclude that the use of a common control plasmid does indeed improve comparability of BCR-ABL mRNA quantification results. However, further standardizing efforts like introducing a calibrator and regular control rounds are needed.

Mechanisms of action of the carcinogenic heterocyclic amine PhIP.

Formed during the cooking of meat, the heterocyclic amine 2-amino-1-methyl-6-phenylimidazo[4-5-b]pyridine (PhIP) is mutagenic and carcinogenic. Although the metabolism and mutational effects of PhIP are well defined, the early cellular and genomic events by which it can induce neoplastic transformation are not yet fully characterised. These early cellular responses to genotoxic doses of PhIP were examined in a human mammary epithelial cell, MCF10A. Using Western blotting, PhIP was shown to induce expression of the DNA damage response proteins p53 and p21(WAF1/CIP1), and to inhibit cell growth while activating G1 cell cycle checkpoint, a consequence of PhIP-induced DNA damage. Using low doses of PhIP (previously shown to activate oestrogenic signalling), PhIP increased proliferation in the oestrogen receptor (ER)-negative MCF10A cell line and to activate the mitogen-activated protein kinase (MAPK) pathway. Inhibition of this pathway significantly reduced the PhIP-induced cell growth of MCF10A cells. The work presented here suggests that, further to its genotoxic properties, at levels close to human exposure PhIP stimulates cellular signalling pathways that are linked to the promotion and progression of neoplastic disease. It is possible that a combination of these DNA damaging and growth promoting properties provide a mechanism for the tumourigenicity of PhIP, and may be key determinants for the tissue specificity of PhIP-induced carcinogenesis.

Biophysical and biological studies of end-group-modified derivatives of Pep-1.

Pep-1 is a tryptophane-rich cell-penetrating peptide (CPP) that has been previously proposed to bind protein cargoes by hydrophobic assembly and translocate them across cellular membranes. To date, however, the molecular mechanisms responsible for cargo binding and translocation have not been clearly identified. This study was conducted to gain insight into the interaction between Pep-1 with its cargo and the biological membrane to identify the thereby involved structural elements crucial for translocation. We studied three peptides differing in their N- and C-termini: (i) Pep-1, carrying an acetylated N-terminus and a C-terminal cysteamine elongation, (ii) AcPepWAmide, with an acetylated N-terminus and an amidated C-terminus, and (iii) PepW, with two free termini. Thioredoxin (TRX) and beta-galactosidase were used as protein cargoes. To study CPP-membrane interactions, we performed biophysical as well as biological assays. To mimic biological membranes, we used phospholipid liposomes in a dye leakage assay and surfactant micelles for high-resolution NMR studies. In addition, membrane integrity, cell viability, and translocation efficiency were analyzed in HeLa cells. An alpha-helical structure was found for all peptides in the hydrophobic N-terminal region encompassing residues 4-13, whereas the hydrophilic region remained unstructured in the presence of micelles. Our results show that the investigated peptides interacted with the micelles as well as with the protein cargo via their tryptophan-rich domain. All peptides displayed an orientation parallel to the micelle surface. The C-terminal cysteamine group formed an additional membrane anchor, leading to more efficient translocation properties in cells. No membrane permeabilization was observed, and our data were largely compatible with an endocytic pathway for cellular uptake.

Acute compartment syndrome following intramedullary pulse lavage and débridement for osteomyelitis of the tibia.

The implantation of gentamicin loaded polymethylmethacrylate (PMMA) beats and other local antibiotic carriers is a common practice in the treatment of chronic osteomyelitis as is the use of local jet lavage débridement. This article presents the case of a patient with chronic osteomyelitis of the tibia, who had no complication after débridement, intramedullary reaming and pulse lavage without tourniquet but sustained a compartment syndrome 2 weeks later during a second procedure in which an intraoperative tourniquet and pulse lavage were combined.

On the influence of non-enzymatic crosslinking of caseins on the gel strength of yoghurt.

After storage of UHT milk at 37 degrees C resp. 50 degrees C, yoghurt was prepared. For a storage temperature of 37 degrees C, breaking strength of the yoghurt samples increased from 2.7 to 5.8 N with increasing storage duration of the UHT milk. A plateau is reached after 17 days of storage. This increase in breaking strength correlates with a significant increase in non-reducible casein oligomerization from 14% for fresh UHT milk to 25% measured using size exclusion chromatography under reducing and denaturing conditions and calculated as sum of predominantly formed dimers and trimers at the total casein fraction. At a storage temperature of 50 degrees C, a less increase in breaking strength from 2.7 to 4.6 N with a plateau after 17 days was observed while casein oligomerization increased to 63%. After acid hydrolysis, only lysinoalanine and histidinoalanine were detected in the caseinate samples via amino acid analysis. The quantified concentration of lysinoalanine and histidinoalanine could not explain the observed casein oligomerization. Thus, unknown crosslinked amino acids must have been formed during storage, inducing significant changes in the functional properties of milk proteins.

High-energy shock wave treatment of femoral head necrosis in adults.

Adults with Stages I to III osteonecrosis of the femoral head present an overall therapeutic challenge. The objective of the current prospective study was to show the effectiveness of high-energy shock wave therapy in treatment of patients with Association Research Circulation Osseous Stage I to Stage III necrosis of the femoral head by assessing clinical and magnetic resonance imaging results. The current study presents the results of 22 patients with femoral head necrosis 1 year after shock wave treatment. The study population consisted of 10 women and 12 men with an average age of 54.9 years (+/- 12.3). The scores achieved on the visual pain analog scale decreased from 8.5 before treatment to 1.2 after 1 year. Simultaneously, the Harris hip score increased from 43.3 to 92 points. Magnetic resonance imaging visualization of a distinct zone of sclerosis around the necrotic area remaining after treatment with extracorporeal shock wave therapy indicated therapeutic failure. The results obtained so far with high-energy shock wave therapy in these patients suggest that this method may offer an alternative to invasive treatment modalities for femoral head necrosis. A noninvasive and moderately priced method then would be available for the treatment of femoral head necrosis in the early stages of the disease process.

Hydrofluoric acid burns of the eye.

A case of hydrofluoric acid (HF) burns of the eye is reported and a review is presented of our investigation into the mechanism of HF toxicity in ocular tissues. A number of therapeutic procedures that have been successful in the treatment of HF skin burns were studied in the rabbit for use in the eye. Immediate single irrigation with water, normal saline or isotonic magnesium chloride solution is the most effective therapy for ocular HF burns. Extrapolation of other skin burn treatments to use in the eye is unacceptable due to the toxicity of these agents in normal eyes and the additive damage caused in burned eyes.

A simple conjunctival biopsy.

Biopsy of conjunctival goblet cells may be carried out by pressing a piece of Millipore filter on the conjunctival surface. This can then be stained with PAS and hematoxylin and observed under the microscope after the filter has been cleared with oil. Either spots of mucous corresponding to the openings of the goblet cells are seen, or the filter adheres to the surface and pulls off one or more layers of epithelial cells and goblet cells. The procedure can be carried out on the unanesthetized eye and does not cause discomfort.