Ambient-temperature time-dependent deformation of cast and additive manufactured Al-Cu-Mg-Ag-TiB2 (A205).

A dual-stage indentation test at ambient temperature including a constant indentation load rate followed by a constant indentation load-hold segment was employed to assess the time-dependent plastic deformation of cast and additive manufactured Al-Cu-Mg-Ag-TiB2 alloys in as-fabricated and T7 conditions at room temperature. Optical microscopy, scanning electron microscopy, electron backscattered diffraction, and transmission electron microscopy techniques were used to study the microstructure of the samples and to correlate the microstructure with the creep properties. That is, the indentation load/displacement/time data from depth-sensing indentation creep were combined with the advanced microstructural assessments to analyze the controlling mechanisms of creep in as-cast, as-built, and T7 samples. Expectedly, the microstructure of samples manufactured by different methods was substantially different in terms of the grain size and the distribution of TiB2 particles. The θ'', θ' and Ω phase were formed in all heat-treated samples; however, the density of Ω phase was higher in the cast-T7 samples. Distinct microstructure and precipitation density resulted in different indentation-derived properties, both cast and AM samples at T7 condition showed enhanced creep resistance compared to their as-manufactured counterparts. The main controlling mechanism of creep deformation was found to be dislocation creep based on the indentation-derived creep stress exponent values.

Next Generation of SiFAlin-Based TATE Derivatives for PET Imaging of SSTR-Positive Tumors: Influence of Molecular Design on In Vitro SSTR Binding and In Vivo Pharmacokinetics.

The Silicon-Fluoride-Acceptor (SiFA)-(18)F-labeling strategy has been shown before to enable the straightforward and efficient (18)F-labeling of complex biologically active substances such as proteins and peptides. Especially in the case of peptides, the radiolabeling proceeds kit-like in short reaction times and without the need of complex product workup. SiFA-derivatized, (18)F-labeled Tyr(3)-octreotate (TATE) derivatives demonstrated, besides strong somatostatin receptor (SSTR) binding, favorable in vivo pharmacokinetics as well as excellent tumor visualization by PET imaging. In this study, we intended to determine the influence of the underlying molecular design and used molecular scaffolds of SiFAlin-TATE derivatives on SSTR binding as well as on the in vivo pharmacokinetics of the resulting (18)F-labeled peptides. For this purpose, new SiFAlin-(Asp)n-PEG1-TATE analogs (where n = 1-4) were synthesized, efficiently radiolabeled with (18)F in a kit-like manner and obtained in radiochemical yields of 70-80%, radiochemical purities of ≥97%, and nonoptimized specific activities of 20.1-45.2 GBq/µmol within 20-25 min starting from 0.7-1.5 GBq of (18)F. In the following, the radiotracer's lipophilicities and stabilities in human serum were determined. Furthermore, the SSTR-specific binding affinities were evaluated by a competitive displacement assay on SSTR-positive AR42J cells. The obtained in vitro results support the assumption that aspartic acids are able to considerably increase the radiotracer's hydrophilicity and that their number does not affect the SSTR binding potential of the TATE derivatives. The most promising tracer (18)F-SiFAlin-Asp3-PEG1-TATE [(18)F]6 (LogD = -1.23 ± 0.03, IC50 = 20.7 ± 2.5 nM) was further evaluated in vivo in AR42J tumor-bearing nude mice via PET/CT imaging against the clinical gold standard (68)Ga-DOTATATE as well as the previously developed SiFAlin-TATE derivative [(18)F]3. The results of these evaluations showed that [(18)F]6-although showing very similar chemical and in vitro properties to [(18)F]3-exhibits not only a slowed renal clearance compared to [(18)F]3, but also a higher absolute tumor uptake compared to (68)Ga-DOTATATE, and furthermore enables excellent tumor visualization with high image resolution. These results emphasize the importance of systematic study of the influence of molecular design and applied structure elements of peptidic radiotracers, as these may considerably influence in vivo pharmacokinetics while not affecting other parameters such as radiochemistry, lipophilicity, serum stability, or receptor binding potential.

Rise in rifampicin-monoresistant tuberculosis in Western Cape, South Africa.

SETTING: Brewelskloof Hospital, Western Cape, South Africa. OBJECTIVES: To verify the perceived increase in rifampicin monoresistant tuberculosis (RMR-TB) in the Cape Winelands-Overberg region and to identify potential risk factors. DESIGN: A retrospective descriptive study of trends in RMR-TB over a 5-year period (2004-2008), followed by a case-control study of RMR and isoniazid (INH) monoresistant TB cases, diagnosed from April 2007 to March 2009, to assess for risk factors. RESULTS: The total number of RMR-TB cases more than tripled, from 31 in 2004 to 98 in 2008. The calculated doubling time was 1.63 years (95%CI 1.18-2.66). For the assessment of risk factors, 95 RMR-TB cases were objectively verified on genotypic and phenotypic analysis. Of 108 specimens genotypically identified as RMR cases, 13 (12%) were misidentified, multidrug-resistant TB. On multivariate analysis, previous use of antiretroviral therapy (OR 6.4, 95%CI 1.3-31.8), alcohol use (OR 4.8, 95%CI 2.0-11.3) and age ≥ 40 years (OR 5.8, 95%CI 2.4-13.6) were significantly associated with RMR-TB. CONCLUSION: RMR-TB is rapidly increasing in the study setting, particularly among patients with advanced human immunodeficiency virus (HIV) disease. Routine drug susceptibility testing should be considered in all TB-HIV co-infected patients, and absence of INH resistance should be confirmed phenotypically if genotypic RMR-TB is detected.

[Overcoming of radiation resistances]. / Strahlenresistenzen und ihre Überwindung.

Despite good achievements in prevention and control, cancer is still a leading cause of death worldwide. The development of resistances against conventional treatment modalities is one of the main causes of failure in the treatment of cancer. Radio- and chemotherapies fail frequently due to intrinsic or acquired resistances in apoptotic signalling pathways or alterations in DNA-repair processes. Targeted radiotherapies employing α-particle-emitting radionuclides and Auger-emitting electrons are a promising approach in cancer treatment to break radio- and chemoresistance by overcoming DNA-repair mechanisms and reversing deficient activation of apoptotic pathways in cancer cells.