The Effect of Fluorination in Manipulating the Nanomorphology in PTB7:PC71BM Bulk Heterojunction Systems

The best performing low bandgap copolymers PTB series to date which is based on thieno[3,4‐b]thiophene‐alt‐benzodithiophene units blended with [6,6]‐phenyl‐C71‐butyric acid methyl ester (PC₇₁BM), have been the focus of polymer‐based solar cells. Here, novel fluorinated polymers PTB7‐Fx (fluorine units coupled with submonomer thieno[3,4‐b]thiophene) with varied degree of fluorination are used as electron donor materials. The PTB7‐Fx:PC₇₁BM bulk heterojunction (BHJ) films spin‐coated from the host solvent chlorobenzene without and with solvent additive 1,8‐diiodooctane (DIO) and the corresponding solar cell devices are systematically investigated to address the morphology‐efficiency relationship. Self‐assembled BHJ morphology is already observed for as‐spun blend films. After adding the solvent additive DIO, the pronounced ordered structures are suppressed and better intermixed films with much smaller domain sizes result. Full fluorination of the third C‐atom of thienothiophene gives rise to the highest power conversion efficiency. As the absorption properties, film morphology and crystallinity remain similar for different degrees of fluorination, the main influence of the photovoltaic performance is ascribed to the different lowest unoccupied molecular orbital (LUMO) of each polymer instead of the film morphology. Thus the device performance can be efficiently improved by tuning the energy level of the polymer without necessarily changing either the film nanomorphology or crystallinity dramatically.     

High stability and no fitness costs of the resistance of codling moth to Cydia pomonella granulovirus (CpGV-M)

Resistance against the biocontrol agent Cydia pomonella granulovirus (CpGV-M) was previously observed in field populations of codling moth (CM, C. pomonella) in South-West Germany. Incidental observations in a laboratory reared field colony (CpR) indicated that this resistance is rather stable, even in genetically heterogeneous CM colonies consisting of both susceptible and resistant individuals. To test this hypothesis, the resistance level of CpR that was 1000times less susceptible to CpGV-M was followed for more than 60 generations of rearing. Even without virus selection pressure, the high level of resistance, expressed as median lethal concentration, remained stable for more than 30 generations and declined only by a factor of 10 after 60 generations. When cohorts of the F32 and F56 generations of the same colony were selected to CpGV-M for five and two generations, respectively, the resistance level increased to factor of >1,000,000 compared to a susceptible control colony. Laboratory reared colonies of CpR, did not exhibit any measurable fitness costs under laboratory conditions in terms of fecundity and fertility. Resistance testing of seven selected codling moth field populations collected between 2003 and 2008 in commercial orchards in Germany that were repeatedly sprayed with CpGV products gave evidence of different levels of resistance and a more than 20-fold increase of the resistance in 1-3years when selection by CpGV-M was continued. A maximum 1,000,000-fold level of resistance to CpGV-M that could be induced in the laboratory under virus pressure had been also observed in one field population. The high stability of resistance observed in the genetically heterogenous colony CpR indicates that resistance to CpGV-M is not very costly.     

Regulation of Helicobacter pylori adherence by gene conversion

Genetic diversification of Helicobacter pylori adhesin genes may allow adaptation of adherence properties to facilitate persistence despite host defences. The sabA gene encodes an adhesin that binds sialyl‐Lewis antigens on inflamed gastric tissue. We found variability in the copy number and locus of the sabA gene and the closely related sabB and omp27 genes due to gene conversion among 51 North American paediatric H. pylori strains. We determined that sabB to sabA gene conversion is predominantly the result of intra‐genomic recombination and RecA, RecG and AddA influence the rate at which it occurs. Although all clinical strains had at least one sabA gene copy, sabA and sabB were lost due to gene conversion at similar rates in vitro, suggesting host selection to maintain the sabA gene. sabA gene duplication resulted in increased SabA protein production and increased adherence to sialyl‐Lewis antigens and mouse gastric tissue. In conclusion, gene conversion is a mechanism for H. pylori to regulate sabA expression level and adherence.     

Rapid inactivation of <Emphasis Type="Italic">Cronobacter sakazakii</Emphasis> on copper alloys following periods of desiccation stress

Cronobacter spp. have been identified as the causative agent in meningitis and necrotizing enterocolitis in premature infants which can be linked to the bacterium's desiccation resistance and persistence in powdered infant formula. In this study we examined the efficacy of copper cast alloys in contact killing of Cronobacter sakazakii following periods of desiccation stress. Cronobacter sakazakii cells suspended in Tryptic Soy Broth (TSB) were killed within 10 min while kept moist on 99.9% copper alloys and within 1 min of drying on 99.9% copper alloys. Survival times were unchanged after cells suspended in TSB were desiccated for 33 days. Cronobacter sakazakii cells suspended in infant formula were killed within 30 min under moist conditions and within 3 min of drying on 99.9% copper alloys. However, when desiccated in infant formula for 45 days, survival times decreased to 10 and 1 min in moist and dry conditions, respectively. In contrast, no decrease in viable cells was noted on stainless steel surfaces under the experimental conditions employed in this study. Cronobacter sakazakii was rapidly killed on copper alloys under all testing conditions of this study indicating that desiccation and copper ion resistance do not prolong survival. These results could have important implications for the utilization of copper in the production and storage of powdered infant formula.     

Moderate chemical modifications of WAY-100635 improve the selectivity for 5-HT1A versus D4 receptors

The selectivity for 5-HT(1A) versus D(4) receptors is significantly increased when the basic side chain of WAY-100635 is replaced by a 4-phenylpiperazine (3e) or a 4-phenyl-1,2,3,6-tetrahydropyridine moiety (3i). The 4-phenyl-1,2,3,6-tetrahydropyridine compounds (3i-l) have a higher affinity for 5-HT(1A) receptors than do the corresponding unsubstituted phenylpiperazine analogues (3e-h). Compounds 3e and 3i appear to be selective for 5-HT(1A) receptors over other relevant receptors and still behave as neutral antagonists.     

Discovery of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221) as a functional antagonist of the apelin (APJ) receptor

The recently discovered apelin/APJ system has emerged as a critical mediator of cardiovascular homeostasis and is associated with the pathogenesis of cardiovascular disease. A role for apelin/APJ in energy metabolism and gastrointestinal function has also recently emerged. We disclose the discovery and characterization of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221), a potent APJ functional antagonist in cell-based assays that is >37-fold selective over the closely related angiotensin II type 1 (AT1) receptor. ML221 was derived from an HTS of the ～330,600 compound MLSMR collection. This antagonist showed no significant binding activity against 29 other GPCRs, except to the κ-opioid and benzodiazepinone receptors (<50/<70%I at 10 μM). The synthetic methodology, development of structure–activity relationship (SAR), and initial in vitro pharmacologic characterization are also presented.     

Lack of ceruloplasmin expression alters aspects of copper transport to the fetus and newborn, as determined in mice

Copper transport and accumulation were studied in virgin and lactating C57BL/6 mice, with and without expression of ceruloplasmin (Cp), to assess the importance of Cp to these processes. One hour after i.p. injection of tracer ⁶⁴Cu, liver and kidney accounted for 80% of the radioactivity, and mammary gland 1%, while in lactating Cp+/+ mice 2–4 days post partum, uptake by mammary gland was 9-fold higher and that of liver and other organs was decreased, with ⁶⁴Cu rapidly appearing in milk. Parallel studies in Cp−/− mice (siblings from same colony) gave virtually identical results. However, their milk contained less ⁶⁴Cu, and actual copper contents determined by furnace atomic absorption were less than half those for milk from normal dams. Liver copper concentrations of pups born to Cp−/− dams also were half those of pups from wild type dams. Copper in pup brains was unaffected; but iron concentrations were reduced. We conclude that absence of Cp, while not affecting entry of exchangeable copper from the blood into the mammary gland, does have a significant effect on the availability of this metal to the newborn through the milk and in the form of stores accumulating in gestation.