The role of the peripherin/RDS gene in retinal dystrophies

The effect of a potent endogenous antioxidant, the pineal gland indole melatonin (MLT) on the mutagenicity of twelve well-known mutagens and carcinogens has been investigated using two in vitro tests the Ames test and the single cell gel electrophoresis assay (SCGE assay or COMET assay). The 12 mutagens used were 7, 12-dimethylbenz(a)anthracene (DMBA), benzo(a)pyrene (BP), 2-aminofluorene (AF), 1,2-dimethylhydrazine (DMH), bleomycin, cyclophosphamide (CP), 4-nitroquinoline-N-oxide (NQO), 2,4, 7-trinitro-9-fluorenone (TNF), 9-aminoacridine (AA), N-nitrosomethylurea (NMU), mitomycin C and sodium azide tested in the absence or in the presence of S9 mix. MLT alone turned out neither toxic nor mutagenic in the Ames test and revealed clastogenic activity at the highest concentration tested (100 microM) in the SCGE assay. In four Salmonella typhimurium tester strains TA 97, TA 98, TA 100 and TA 102 MLT significantly reduced the mutagenicity of chemicals which require S9 activation. In the SCGE assay performed on CHO cells, preincubation with MLT led to a strong inhibition of clastogenic activities of DMBA and CP, and in a lesser extent with BP and NMU. With mitomycin C, MLT exacerbated responses in both tests. The possible mechanisms of MLT's inhibitory action are discussed.     

Implementation of evolutionary fuzzy systems

Evolutionary fuzzy systems are discussed in which the membership function shapes and types and the fuzzy rule set including the number of rules inside it are evolved using a genetic (evolutionary) algorithm. In addition, the genetic parameters (operators) of the evolutionary algorithm are adapted via a fuzzy system. Benefits of the methodology are illustrated in the process of classifying the iris data set. Possible extensions of the methods are summarized     

Optically-induced charge storage in self-assembled InAs quantum dots

We present results on spectrally resolved photo-resistance studies of optically-induced charge storage effects in self-organized InAs quantum dots (QDs). The stored charge can be detected and erased electrically. The investigated structure designed for electron or hole storage in the QDs consists of a modulation doped two-dimensional channel which was grown on top of a layer of InAs QDs, separated by an asymmetric tunnel barrier. Our results show that optical QD charging with spectral resolution provides information on the charging dynamics and on the quantity and spectral dependence of stored charges in the QDs. This is a novel technique by which QD excitation spectra can be studied. Spectrally resolved storage effect measurements on electrons as well as on holes allowed to investigate thermal redistribution of carriers in the quantum dot layer. It was found that only at low temperatures carriers can be stored selectively over long time scales in the InAs QDs. The charge storage effect is observable for several hours at temperatures up to 170 K, for several seconds up to 250 K due to an increase in thermal emission of stored charges.     

Effects of bedding with recycled sand on lying behaviors,udder hygiene,and preference of lactating Holstein dairy cows

Effects of bedding with recycled sand and season on lying behaviors, hygiene, and preferences of late-lactation Holstein cows were studied. It was hypothesized that recycled sand will decrease lying time and increase hygiene scores due to increased moisture content and organic matter, and thus a preference for the control sand will be evident. Cows (n = 64) were divided into 4 groups (n = 8 per group) per season. In summer (August to September), cows were balanced by days in milk (268.1 ± 11.9 d) and parity (2.0 ± 0.2). In winter (January to February), mean DIM was 265.5 ± 34.1 d. Cows were assigned to 1 of 2 treatments using a crossover design with each treatment lasting 7 d (no-choice phase): bedding with recycled sand (RS; n = 32) or control (CO; clean sand; n = 32). Stocking density was maintained at 100%. The choice phase allowed cows to have access to either treatment with stocking density at 50%. Accelerometers recorded daily lying time, number of lying bouts per day, lying bout duration (min/bout), and total steps per day. Teat swabs, milk, sand samples, and udder hygiene scores were collected on d 0, 3, and 7 of each experimental week. Samples were cultured for streptococci, staphylococci, and gram-negative bacteria. Video data were used to assess bedding preferences. All data were analyzed using the MIXED and GLIMMIX procedures of SAS 9.4 (SAS Institute Inc., Cary, NC). Lying time was not affected by treatment, but cows did take more steps during winter. Bacterial counts were elevated for cows on recycled sand. A preference was observed for clean sand during the summer, but no preference was observed for sand during the winter. Regardless of bedding, the most commonly observed behavior was lying in the stalls, which suggested either bedding might be suitable. Caution should be used with this interpretation of preference, as sand was recycled only once. This limited reclamation was still sufficient to potentially alter the composition of sand, driving the observed preference. If these changes in composition continue, then the strength of the preference may also change. However, considering all variables within the current study, recycled sand is a viable bedding source to use for dairy cows.     

NGS Analysis Confirms Common TP53 and RB1 Mutations,and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas

Ocular adnexal (OA) sebaceous carcinomas generally demonstrate more aggressive clinical and histopathological phenotypes than extraocular cases, but the molecular drivers implicated in their oncogenesis remain poorly defined. A retrospective review of surgical and ocular pathology archives identified eleven primary resection specimens of OA sebaceous carcinomas with adequate tissue for molecular analysis; two extraocular cases were also examined. Next-generation sequencing was used to evaluate mutations and copy number changes in a large panel of cancer-associated genes. Fluorescence in situ hybridization (FISH) confirmed MYC copy number gain in select cases, and immunohistochemistry to evaluate MYC protein expression. The commonest mutations occurred in TP53 (10/13) and RB1 (7/13). Additional mutations in clinically actionable genes, or mutations with a frequency of at least 25%, included the NF1 (3/12), PMS2 (4/12), ROS1 (3/12), KMT2C (4/12), MNX1 (6/12), NOTCH1 (4/12), PCLO (3/12), and PTPRT (3/12) loci. Low level copy number gain suggestive of amplification of the MYC locus was seen in two cases, and confirmed using FISH. MYC protein expression, as assessed by immunohistochemistry, was present in almost all sebaceous carcinoma cases. Our findings support the concept that alterations in TP53 and RB1 are the commonest alterations in sebaceous carcinoma, and suggest that MYC may contribute to the oncogenesis of these tumors.     

Looking for design in materials design

Despite great advances in computation, materials design is still science fiction. The construction of structure-property relations on the quantum scale will turn computational empiricism into true design.     

A Highly Translatable Dual-arm Local Delivery Strategy To Achieve Widespread Therapeutic Coverage in Healthy and Tumor-bearing Brain Tissues

Drug delivery nanoparticles (NPs) based entirely on materials generally recognized as safe that provide widespread parenchymal distribution following intracranial administration via convection-enhanced delivery (CED) are introduced. Poly(lactic-co-glycolic acid) (PLGA) NPs are coated with various poloxamers, including F68, F98, or F127, via physical adsorption to render particle surfaces non-adhesive, thereby resisting interactions with brain extracellular matrix. F127-coated PLGA (F127/PLGA) NPs provide markedly greater distribution in healthy rat brains compared to uncoated NPs and widespread coverage in orthotopically-established brain tumors. Distribution analysis of variously-sized F127/PLGA NPs determines the average rat brain tissue porosity to be between 135 and 170 nm while revealing unprecedented brain coverage of larger F127/PLGA NPs with an aid of hydraulic pressure provided by CED. Importantly, F127/PLGA NPs can be lyophilized for long-term storage without compromising their ability to penetrate the brain tissue. Further, 65- and 200-nm F127/PLGA NPs lyophilized-reconstituted and administered in a moderately hyperosmolar infusate solution show further enhance particle dissemination in the brain via osmotically-driven enlargement of the brain tissue porosity. Combination of F127/PLGA NPs and osmotic tissue modulation provides a means with a clear regulatory path to maximize the brain distribution of large NPs that enable greater drug loading and prolong drug release.