Polyelectrolyte multilayer assembly bearing ketoprofen for transdermal delivery

A novel microencapsulation technology based on layer-by-layer assembly has been extensively studied and used for controlled delivery of drug microcrystal having poor aqueous solubility and low bioavailability. A non-steroidal anti-inflammatory drug ketoprofen (KF)was selected for encapsulation using biodegradable and biocompatible polyions and synergistically the fabricated system was embedded in gel matrix for topical application. Topical application of the drugs at the pathological sites offer potential advantages of delivering the drug directly to the site of action and thus producing high tissue concentrations of the drug

Biodiesel: Freedom from Dependence on Fossil Fuels?

In view of the depleting oil reserves and exponential rise in petroleum prices, the search for alternative sources of fuel is very timely and important. The present paper addresses the underlying issues in biodiesel production from biomaterials and sustainable production and supply of first-generation biofuels, especially the one from jatropha. The agencies and research institutions involved in the production of biofuels and the national and international efforts made in this regard are discussed here. There is also a dire need of a step towards large-scale production and supply of second-generation biofuels, although in infant stage, to strengthen the world economy in general and Indian economy in particular. However, the production of biofuels are likely to have serious socio-economic implications especially to the lesser developed societies. This needs serious attention from policy makers and public at large

THE LIVING CASE: SEARCHING FOR A DEEPER STRUCTURE IN THE CASE ANALYSIS PROCESS

One of the primary methods of instruction in business disciplines is the case. However, in its current form of written presentation, some of the basic learning goals associated with case instruction are compromised. We have used new forms of media involving computing and communication to build a novel learning environment, the Living Case, which flexibly and interactively presents cases along with provide dynamic, on-going feedback to students analyzing a case. In our research we have formalized the process of analyzing a case in order to recognize and interpret student analysis behavior so that provide relevant assistance can be provided. Case analysis is characterized as a problem solving activity driven by comprehension and reasoning operators. A search for these operators led us to build an inventory of reading activities. Twelve hours of protocols are analyzed using "retelling profiles" as an interpretation mechanism. Retelling profiles are visual time plots of the activities undertaken in a reading task. Our preliminary results suggest a deeper structure to case analysis which is common across business disciplines, cases, and individuals. Differences between the analysis strategies of experts and novices are also formalized. Finally, an expert's analogical reasoning strategy using task-specific knowledge encoded as "templates" is identified as a major contributor to their efficiency in solving cases. Templates of typical company situations and responses are triggered early in the analysis process, and subsequent data gathering and reasoning is directed by an attempt to apply the template to the case situation.Information Systems Working Papers Serie

THE LIVING CASE: SEARCHING FOR A DEEPER STRUCTURE IN THE CASE ANALYSIS PROCESS

One of the primary methods of instruction in business disciplines is the case. However, in its current form of written presentation, some of the basic learning goals associated with case instruction are compromised. We have used new forms of media involving computing and communication to build a novel learning environment, the Living Case, which flexibly and interactively presents cases along with provide dynamic, on-going feedback to students analyzing a case. In our research we have formalized the process of analyzing a case in order to recognize and interpret student analysis behavior so that provide relevant assistance can be provided. Case analysis is characterized as a problem solving activity driven by comprehension and reasoning operators. A search for these operators led us to build an inventory of reading activities. Twelve hours of protocols are analyzed using "retelling profiles" as an interpretation mechanism. Retelling profiles are visual time plots of the activities undertaken in a reading task. Our preliminary results suggest a deeper structure to case analysis which is common across business disciplines, cases, and individuals. Differences between the analysis strategies of experts and novices are also formalized. Finally, an expert's analogical reasoning strategy using task-specific knowledge encoded as "templates" is identified as a major contributor to their efficiency in solving cases. Templates of typical company situations and responses are triggered early in the analysis process, and subsequent data gathering and reasoning is directed by an attempt to apply the template to the case situation.Information Systems Working Papers Serie

Dual Molecular Signals Mediate the Bacterial Response to Outer-Membrane Stress

In Gram-negative bacteria, outer-membrane integrity is essential for survival and is monitored by the σ[superscript E] stress-response system, which initiates damage-repair pathways. One activating signal is unassembled outer-membrane proteins. Using biochemical and genetic experiments in Escherichia coli, we found that off-pathway intermediates in lipopolysaccharide transport and assembly provided an additional required signal. These distinct signals, arising from disruptions in the transport and assembly of the major outer-membrane components, jointly determined the rate of proteolytic destruction of a negative regulator of the σ[superscript E] transcription factor, thereby modulating the expression of stress-response genes. This dual-signal system permits a rapid response to dysfunction in outer-membrane biogenesis, while buffering responses to transient fluctuations in individual components, and may represent a broad strategy for bacteria to monitor their interface with the environment.National Institutes of Health (U.S.) (Grant AI-16892)National Institutes of Health (U.S.) (Grant GM-36278

Inactivation of Cone-Specific Phototransduction Genes in Rod Monochromatic Cetaceans

Vertebrate vision is mediated by two types of photoreceptors, rod and cone cells. Rods are more sensitive than cones in dim light, but are incapable of color discrimination because they possess only one type of photosensitive opsin protein (rod opsin = RH1). By contrast, cones are more important for vision in bright light. Cones also facilitate dichromatic color vision in most mammals because there are two cone pigment genes (SWS1, LWS) that facilitate color discrimination. Cone monochromacy occurs when one of the cone opsins (usually SWS1) is inactivated and is present in assorted subterranean, nocturnal, and aquatic mammals. Rod monochromacy occurs when both cone photoreceptors are inactivated, resulting in a pure rod retina. The latter condition is extremely rare in mammals and has only been confirmed with genetic evidence in five cetacean lineages, golden moles, armadillos, and sloths. The first genetic evidence for rod monochromacy in these taxa consisted of inactivated copies of both of their cone pigment genes (SWS1, LWS). However, other components of the cone phototransduction cascade are also predicted to accumulate inactivating mutations in rod monochromats. Here, we employ genome sequences and exon capture data from four baleen whales (bowhead, two minke whales, fin whale) and five toothed whales (sperm whale, Yangtze River dolphin, beluga, killer whale, bottlenose dolphin) to test the hypothesis that rod monochromacy is associated with the inactivation of seven genes (GNAT2, GNB3, GNGT2, PDE6C, PDE6H, CNGA3, CNGB3) in the cone phototransduction cascade. Cone-monochromatic toothed whales that retain a functional copy of LWS (beluga whale, Yangtze River dolphin, killer whale, bottlenose dolphin) also retain intact copies of other cone-specific phototransduction genes, whereas rod monochromats (Antarctic minke whale, common minke whale, fin whale, bowhead whale, sperm whale) have inactivating mutations in five or more genes in the cone phototransduction cascade. The only shared inactivating mutations that were discovered occur in the three Balaenoptera species (two minke whales, fin whale), further suggesting that rod monochromacy evolved independently in two clades of baleen whales, Balaenopteroidea and Balaenidae. We estimate that rod monochromacy evolved first in Balaenopteroidea (∼28.8 Ma) followed by P. macrocephalus (∼19.5 Ma) and Balaenidae (∼13.0 Ma)

Inhibition of the mammalian target of rapamycin (mTOR) in advanced pancreatic cancer: results of two phase II studies

<p>Abstract</p> <p>Background</p> <p>The phosphoinositide 3-kinase (PI3K)/Akt pathway is constitutively activated in pancreatic cancer and the mammalian target of rapamycin (mTOR) kinase is an important mediator for its signaling. Our recent <it>in vitro </it>studies suggest that prolonged exposure of pancreatic cancer cells to mTOR inhibitors can promote insulin receptor substrate-PI3K interactions and paradoxically increase Akt phosphorylation and cyclin D1 expression in pancreatic cancer cells (negative feedback loop). The addition of erlotinib to rapamycin can down-regulate rapamycin-stimulated Akt and results in synergistic antitumor activity with erlotinib in preclinical tumor models.</p> <p>Methods</p> <p>Two studies prospectively enrolled adult patients with advanced pancreatic cancer, Eastern Cooperative Oncology Group performance status 0-1, adequate hematologic, hepatic and renal parameters and measurable disease. In Study A, temsirolimus was administered intravenously at 25 mg weekly. In Study B, everolimus was administered orally at 30 mg weekly and erlotinib was administered at 150 mg daily. The primary endpoint in both studies was overall survival at 6 months. Secondary endpoints included time to progression, progression-free survival, overall survival, response rate, safety and toxicity. Pretreatment tumor biopsies were analyzed by immunofluorescence and laser scanning cytometry for the expression of pmTOR/mTOR, pAkt/Akt, pErk/Erk, pS6, p4EBP-1 and PTEN.</p> <p>Results</p> <p>Five patients enrolled in Study A; Two patients died within a month (rapid disease progression and hemorrhagic stroke, respectively). One patient developed dehydration and another developed asthenia. Sixteen patients enrolled in Study B.: 12 males, all ECOG PS = 1. Median cycles = 1 (range 1-2). Grade 4 toxicity: hyponatremia (n = 1), Grade 3: diarrhea (n = 1), cholangitis (n = 3), hyperglycemia (n = 1), fatigue (n = 1). Grade 2: pneumonia (n = 2), dehydration (n = 2), nausea (n = 2), neutropenia (n = 1), mucositis (n = 2) & rash (n = 2). Four patients were hospitalized. Progressive disease occurred in 15 and 1 was non-evaluable. Pretreatment biopsies revealed a higher pAkt/Akt ratio in tumor specimens that in nonmalignant pancreatic tissue. No such trends were noted for the other biomarkers.</p> <p>Conclusions</p> <p>Neither study with mTOR inhibitors demonstrated objective responses or disease stability. The negative feedback loop resulting from mTOR inhibition may account for the disease progression and toxicity noted in these studies. Future strategies should aim for a broader targeting of the PI3K pathway in pancreatic cancer.</p> <p>Trial Registration</p> <p><b>Trial registration: Study A</b>: NCT 0075647. <b>Study B</b>: NCT00640978</p