Drug-resistant Streptococcus pneumoniae: the beginning of the end for many antibiotics?

The antiinflammatory activity of topically applied sertaconazole nitrate was investigated. The dermal administration of 2% sertaconazole to rats, in which edema was induced by application of croton oil in the external ear, induced a 39.8% reduction of edema. The results show that sertaconazole applied by topical route at the concentration at which it is used in clinic, has antiinflammatory action in this experimental model.     

Carbon fiber reinforced ceramic matrix composites with an oxidation resistant boron nitride interface coating

Toughening a ceramic in a ceramic matrix composite (CMC) depends on an ability of the composite to tolerate an accumulation of matrix cracks. When the reinforcement phase is carbon fiber, these cracks leave the fiber susceptible to destructive oxidation by ingress of air during high temperature exposure. Generally, a graphitic carbon interface coating is applied to carbon fibers because it provides for a weak bond between fiber and matrix that is required to promote toughening. This investigation seeks to utilize a BN coating instead of a C coating in order to promote oxidation resistance. Like graphitic carbon, BN is soft and easily cleavable. Preliminary observations that C/BN/SiC CMC's using Toray T300 carbon fibers were highly brittle and of low strength lead to a requirement of heat treating the fibers prior to the CVD of BN for toughened composites to be fabricated. It is likely heat treating removed reactive functionalities from the fiber surface to yield a weakly adhered and compliant interface.     

Investigating LMNA-Related Dilated Cardiomyopathy Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

LMNA-related dilated cardiomyopathy is an inherited heart disease caused by mutations in the LMNA gene encoding for lamin A/C. The disease is characterized by left ventricular enlargement and impaired systolic function associated with conduction defects and ventricular arrhythmias. We hypothesized that LMNA-mutated patients’ induced Pluripotent Stem Cell-derived cardiomyocytes (iPSC-CMs) display electrophysiological abnormalities, thus constituting a suitable tool for deciphering the arrhythmogenic mechanisms of the disease, and possibly for developing novel therapeutic modalities. iPSC-CMs were generated from two related patients (father and son) carrying the same E342K mutation in the LMNA gene. Compared to control iPSC-CMs, LMNA-mutated iPSC-CMs exhibited the following electrophysiological abnormalities: (1) decreased spontaneous action potential beat rate and decreased pacemaker current (I_f) density; (2) prolonged action potential duration and increased L-type Ca²⁺ current (I_Ca,L) density; (3) delayed afterdepolarizations (DADs), arrhythmias and increased beat rate variability; (4) DADs, arrhythmias and cessation of spontaneous firing in response to β-adrenergic stimulation and rapid pacing. Additionally, compared to healthy control, LMNA-mutated iPSC-CMs displayed nuclear morphological irregularities and gene expression alterations. Notably, KB-R7943, a selective inhibitor of the reverse-mode of the Na⁺/Ca²⁺ exchanger, blocked the DADs in LMNA-mutated iPSC-CMs. Our findings demonstrate cellular electrophysiological mechanisms underlying the arrhythmias in LMNA-related dilated cardiomyopathy.     

Direct association of interleukin-6 with a 130-kDa component of the interleukin-6 receptor system

Affinity cross-linking of membrane bound 125I-interleukin-6 (IL-6) on several cell lines revealed a three-band pattern of IL-6-containing cross-linked complexes with molecular masses of 100, 120, and 150 kDa. To identify the membrane components that were associated with IL-6 in the three complexes, we employed the Denny-Jaffe reagent, a heterobifunctional, cleavable cross-linker that allows the transfer of 125I from the ligand to its receptor. Samples cross-linked with Denny-Jaffe reagent were analyzed by two-dimensional SDS-polyacrylamide gel electrophoresis in which the cross-linker was cleaved prior to the second dimension. This analysis revealed that IL-6 directly associates with a 130-kDa membrane protein thus allowing the formation of the 150-kDa complex. In addition, both the 100- and 120-kDa cross-linked complexes were shown to include an 80-kDa membrane glycoprotein associated with one and two IL-6 molecules, respectively.     

Development of species identification in ducklings: III. Maturational rectification of perceptual deficit caused by auditory deprivation.

In 3 experiments, mute Peking ducklings, devocalized as embryos and manipulated in auditory isolation, manifested a selective high-frequency perceptual deficit vis-a-vis the maternal cal of their species at 24 hrs after hatching. Since it takes a rather specific auditory experiential input to rectify this high-frequency insensitivity at 24 hrs, it was predicted that, in the absence of auditory experience, devocal-isolated Ss would fail to show sufficient endogenously mediated improvement to bring them up to the level of perceptual competence of vocal-communal Ss at any age. This hypothesis proved wrong in that the proportion of devocalized Ss showing a preference for the normal maternal call over the >825-Hz attenuated one, became equivalent to the vocal Ss at 48 hrs after hatching, as did their ability to discriminate the normal maternal call from >1,800-Hz attenuated maternal call. At 65 hrs, however, the devocalized Ss' performance deteriorated back to the level observed at 24 hrs. It is concluded that embryonic exposure to the (sibling) contact-contentment call prevents the perceptual deficit at 24 hrs and the deterioration at 65 hrs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Automated provisioning of BGP customers

Manual configuration of IP routers is an expensive, time-consuming, and error-prone process. For large Internet service providers, establishing service for new customers is a major part of the financial cost of running the network. Increasingly, these customers want to exchange routing information with their provider(s) using the border gateway protocol (BGP), a complex and highly programmable interdomain routing protocol. This article describes how a provider can configure its connections to BGP-speaking customers, from the technical questions asked of new customers to the individual configuration commands applied to the production routers. We present a case study of a technical questionnaire and describe how the provider assigns unique identifiers such as IP address blocks, interface names, and access control list numbers on behalf of the customer. Next, we describe an example set of provisioning rules that use the customer-specific information to generate a sequence of configuration commands - a "configlet" - for adding the new connection to the network; our configuration rules are expressed using Cisco Internet Operating System (IOS) commands as an example. Then we describe a database schema for storing and accessing the customer-specific data, and discuss how to use a virtual view on this database to populate a template that captures the syntax of the router commands. Our provisioning system provides an inexpensive, efficient, and accurate way for a provider to configure connections to new BGP-speaking customers.     

Successful ultraviolet B treatment of psoriasis is accompanied by a reversal of keratinocyte pathology and by selective depletion of intraepidermal T cells

Skin irradiation with ultraviolet B (UVB) is a common and often durable treatment for psoriasis and other inflammatory skin disorders. We studied the effects of UVB on keratinocytes and leukocytes in psoriatic tissue and in culture. In nine patients treated repetitively, most of the cellular and molecular changes that typify the psoriatic epidermis reverted to normal. Keratinocyte hyperplasia, assessed by expression of the Ki-67 cell cycle antigen, decreased by 70%, and residual cell proliferation was appropriately confined to the basal layer. Epidermal thickening was reduced by 60%, and a granular layer reformed. Expression of keratin 16, as well as suprabasal integrin alpha 3 and insulin-like growth factor-1 receptors, was eliminated, whereas filagrin increased markedly. UVB also depleted > 90% of the CD3+, CD8+, and CD25+ T cells from the psoriatic epidermis, whereas dermal T cells were only minimally depressed. The latter finding parallels the known inability of these doses of UVB to penetrate the dermis. In tissue culture, UVB was antiproliferative and cytotoxic toward T cells and keratinocytes, but the T cells were 10-fold more sensitive. Furthermore, low doses of UVB induced apoptosis in lymphocytes but not keratinocytes, as detected by the TUNEL (TdT-mediated dUTP-biotin nick end labeling) technique. The selective effects of UVB on intraepidermal T cells in situ and in culture support the hypothesis that epidermal alterations in psoriasis can be normalized by a depletion of activated intraepidermal T cells.