Connexin36 contributes to INS-1E cells survival through modulation of cytokine-induced oxidative stress, ER stress and AMPK activity.

Cell-to-cell communication mediated by gap junctions made of Connexin36 (Cx36) contributes to pancreatic β-cell function. We have recently demonstrated that Cx36 also supports β-cell survival by a still unclear mechanism. Using specific Cx36 siRNAs or adenoviral vectors, we now show that Cx36 downregulation promotes apoptosis in INS-1E cells exposed to the pro-inflammatory cytokines (IL-1β, TNF-α and IFN-γ) involved at the onset of type 1 diabetes, whereas Cx36 overexpression protects against this effect. Cx36 overexpression also protects INS-1E cells against endoplasmic reticulum (ER) stress-mediated apoptosis, and alleviates the cytokine-induced production of reactive oxygen species, the depletion of the ER Ca(2+) stores, the CHOP overexpression and the degradation of the anti-apoptotic protein Bcl-2 and Mcl-1. We further show that cytokines activate the AMP-dependent protein kinase (AMPK) in a NO-dependent and ER-stress-dependent manner and that AMPK inhibits Cx36 expression. Altogether, the data suggest that Cx36 is involved in Ca(2+) homeostasis within the ER and that Cx36 expression is downregulated following ER stress and subsequent AMPK activation. As a result, cytokine-induced Cx36 downregulation elicits a positive feedback loop that amplifies ER stress and AMPK activation, leading to further Cx36 downregulation. The data reveal that Cx36 plays a central role in the oxidative stress and ER stress induced by cytokines and the subsequent regulation of AMPK activity, which in turn controls Cx36 expression and mitochondria-dependent apoptosis of insulin-producing cells.

Universal Design for Better Living: “Where to Get Gadgets and Gizmos”, May 2004

If they don’t carry the item, ask them to order it for you. Look at discount stores, such as Target, Wal-Mart, K-Mart, or Menard’s (they are more likely to carry items with universal design features). Look at the “Gadgets and Gizmos” section of the Iowa State University Extension Web site on “Universal Design & Home Accessibility.”

Evaluation of a Bridge Constructed using High Performance Steel, May 2006

Of the approximately 25,000 bridges in Iowa, 28% are classified as structurally deficient, functionally obsolete, or both. Because many Iowa bridges require repair or replacement with a relatively limited funding base, there is a need to develop new bridge materials that may lead to longer life spans and reduced life-cycle costs. In addition, new and effective methods for determining the condition of structures are needed to identify when the useful life has expired or other maintenance is needed. Due to its unique alloy blend, high-performance steel (HPS) has been shown to have improved weldability, weathering capabilities, and fracture toughness than conventional structural steels. Since the development of HPS in the mid-1990s, numerous bridges using HPS girders have been constructed, and many have been economically built. The East 12th Street Bridge, which replaced a deteriorated box girder bridge, is Iowa’s first bridge constructed using HPS girders. The new structure is a two-span bridge that crosses I-235 in Des Moines, Iowa, providing one lane of traffic in each direction. A remote, continuous, fiber-optic based structural health monitoring (SHM) system for the bridge was developed using off-the-shelf technologies. In the system, sensors strategically located on the bridge collect raw strain data and then transfer the data via wireless communication to a gateway system at a nearby secure facility. The data are integrated and converted to text files before being uploaded automatically to a website that provides live strain data and a live video stream. A data storage/processing system at the Bridge Engineering Center in Ames, Iowa, permanently stores and processes the data files. Several processes are performed to check the overall system’s operation, eliminate temperature effects from the complete strain record, compute the global behavior of the bridge, and count strain cycles at the various sensor locations.

A Simple Access Pricing Rule to Achieve the Ramsey Outcome in Two-Way Access

In this paper, I consider a general and informationally effcient approach to determine the optimal access rule and show that there exists a simple rule that achieves the Ramsey outcome as the unique equilibrium when networks compete in linear prices without network-based price discrimination. My approach is informationally effcient in the sense that the regulator is required to know only the marginal cost structure, i.e. the marginal cost of making and terminating a call. The approach is general in that access prices can depend not only on the marginal costs but also on the retail prices, which can be observed by consumers and therefore by the regulator as well. In particular, I consider the set of linear access pricing rules which includes any fixed access price, the Efficient Component Pricing Rule (ECPR) and the Modified ECPR as special cases. I show that in this set, there is a unique access rule that achieves the Ramsey outcome as the unique equilibrium as long as there exists at least a mild degree of substitutability among networks' services.

Abnormalities of fuel utilization as predisposing to the development of obesity in humans.

A number of recent investigations in man have demonstrated that a low ratio of fat to carbohydrate oxidation (i.e., a high respiratory quotient or RQ) was associated with actual and/or subsequent body weight gain in obese non-diabetic Pima Indians, in American men of various ages and in post-obese European women investigated shortly after the cessation of a hypocaloric diet. It is well known that numerous exogenous and endogenous factors influence the RQ at rest such as: the level of feeding (positive vs. negative energy balance), the composition of food eaten (high vs. low carbohydrate), the size of the glycogen stores, the amount of adipose tissue as well as genetic factors. It should be stressed that some nutritional situations can co-exist during which a low ratio of fat to carbohydrate is observed (i.e., a high RQ) despite weight loss. Furthermore, in most studies mentioned above, the low fat to carbohydrate oxidation ratio explains less than 10% of the variance in weight gain, suggesting that numerous additional factors also play a substantial role in the onset of weight gain. It is concluded that: 1) a low fat to carbohydrate oxidation ratio or an abnormal fat oxidation is difficult to define quantitatively since it is largely influenced by the energy level and the composition of the diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Living Snow Fences, 2006

Blowing snow can cause significant problems for mobility and safety during winter weather in three distinct ways. It may drift onto the road, thus requiring almost continuous plowing while the wind is blowing (which may occur when a given winter storm is over). Snow may drift onto wet pavement (perhaps caused by ice control chemicals) and dilute out the chemicals on the road, creating ice on the road. And sufficient blowing snow can cause a major deterioration in visibility on the road, a factor which has been shown to be significant in winter crashes. The problem of blowing snow can be very effectively addressed by creating a snow storage device upwind of the road that requires protection from snow drifting. Typically, these storage devices are fences. Extensive design guidance exists for the required height and placement of such fences for a given annual snowfall and given local topography. However, the design information on the placement of living snow fences is less complete. The purpose of this report is to present the results of three seasons of study on using standing corn as snow fences. In addition, the experience of using switch grass as a snow storage medium is also presented. On the basis of these experimental data, a design guide has been developed that makes use of the somewhat unique snow storage characteristics of standing corn snow fences. The results of the field tests on using standing corn showed that multiple rows of standing corn store snow rather differently than a traditional wooden snow fence. Specifically, while a traditional fence stores most of the snow downwind from the fence (and thus must be placed a significant distance upwind of the road to be protected, specifically at least 35 times the snow fence height) rows of standing corn store the majority of the snow within the rows. Results from the three winters of testing show that the standing corn snow fences can store as much snow within the rows of standing corn as a traditional fence of typical height for operation in Iowa (4 to 6 feet) can store. This finding is significant because it means that the snow fences can be placed at the edge of the farmer’s field closest to the road, and still be effective. This is typically much more convenient for the farmer and thus may mean that more farmers would be willing to participate in a program that uses standing corn than in traditional programs. ii On the basis of the experimental data, design guidance for the use of standing corn as a snow storage device in Iowa is given in the report. Specifically, it is recommended that if the fetch in a location to be protected is less than 5,000 feet, then 16 rows of standing corn should be used, at the edge of the field adjacent to the right of way. If the fetch is greater than 5,000 feet, then 24 rows of standing corn should be used. This is based on a row spacing of 22 inches. Further, it should be noted that these design recommendations are ONLY for the State of Iowa. Other states of course have different winter weather and without extensive further study, it cannot be said that these guidelines would be effective in other locations with other winter conditions.

Emerging Biofuels: Outlook of Effects on U.S. Grain, Oilseed, and Livestock Markets, 2007

Projections of U.S. ethanol production and its impacts on planted acreage, crop prices, livestock production and prices, trade, and retail food costs are presented under the assumption that current tax credits and trade policies are maintained. The projections were made using a multi-product, multi-country deterministic partial equilibrium model. The impacts of higher oil prices, a drought combined with an ethanol mandate, and removal of land from the Conservation Reserve Program (CRP) relative to baseline projections are also presented. The results indicate that expanded U.S. ethanol production will cause long-run crop prices to increase. In response to higher feed costs, livestock farmgate prices will increase enough to cover the feed cost increases. Retail meat, egg, and dairy prices will also increase. If oil prices are permanently $10-per-barrel higher than assumed in the baseline projections, U.S. ethanol will expand significantly. The magnitude of the expansion will depend on the future makeup of the U.S. automobile fleet. If sufficient demand for E-85 from flex-fuel vehicles is available, corn-based ethanol production is projected to increase to over 30 billion gallons per year with the higher oil prices. The direct effect of higher feed costs is that U.S. food prices would increase by a minimum of 1.1% over baseline levels. Results of a model of a 1988-type drought combined with a large mandate for continued ethanol production show sharply higher crop prices, a drop in livestock production, and higher food prices. Corn exports would drop significantly, and feed costs would rise. Wheat feed use would rise sharply. Taking additional land out of the CRP would lower crop prices in the short run. But because long-run corn prices are determined by ethanol prices and not by corn acreage, the long-run impacts on commodity prices and food prices of a smaller CRP are modest. Cellulosic ethanol from switchgrass and biodiesel from soybeans do not become economically viable in the Corn Belt under any of the scenarios. This is so because high energy costs that increase the prices of biodiesel and switchgrass ethanol also increase the price of cornbased ethanol. So long as producers can choose between soybeans for biodiesel, switchgrass for ethanol, and corn for ethanol, they will choose to grow corn. Cellulosic ethanol from corn stover does not enter into any scenario because of the high cost of collecting and transporting corn stover over the large distances required to supply a commercial-sized ethanol facility.

Mobile termination and mobile penetration

In this paper, we study how access pricing affects network competition when subscription demand is elastic and each network uses non-linear prices and can applytermination-based price discrimination. In the case of a fixed per minute terminationcharge, we find that a reduction of the termination charge below cost has two opposing effects: it softens competition but helps to internalize network externalities. Theformer reduces mobile penetration while the latter boosts it. We find that firms always prefer termination charge below cost for either motive while the regulator preferstermination below cost only when this boosts penetration.Next, we consider the retail benchmarking approach (Jeon and Hurkens, 2008)that determines termination charges as a function of retail prices and show that thisapproach allows the regulator to increase penetration without distorting call volumes.

Competitive location and pricing on networks

In this paper we consider a location and pricing model for a retail firm that wants to enter a spatial market where a competitor firm is already operating as a monopoly with several outlets. The entering firms seeks to determine the optimal uniform mill price and its servers' locations that maximizes profits given the reaction in price of the competitor firm to its entrance. A tabu search procedure is presentedto solve the model together with computational experience.

Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting.

Prolonged deprivation of food induces dramatic changes in mammalian metabolism, including the release of large amounts of fatty acids from the adipose tissue, followed by their oxidation in the liver. The nuclear receptor known as peroxisome proliferator-activated receptor alpha (PPARalpha) was found to play a role in regulating mitochondrial and peroxisomal fatty acid oxidation, suggesting that PPARalpha may be involved in the transcriptional response to fasting. To investigate this possibility, PPARalpha-null mice were subjected to a high fat diet or to fasting, and their responses were compared with those of wild-type mice. PPARalpha-null mice chronically fed a high fat diet showed a massive accumulation of lipid in their livers. A similar phenotype was noted in PPARalpha-null mice fasted for 24 hours, who also displayed severe hypoglycemia, hypoketonemia, hypothermia, and elevated plasma free fatty acid levels, indicating a dramatic inhibition of fatty acid uptake and oxidation. It is shown that to accommodate the increased requirement for hepatic fatty acid oxidation, PPARalpha mRNA is induced during fasting in wild-type mice. The data indicate that PPARalpha plays a pivotal role in the management of energy stores during fasting. By modulating gene expression, PPARalpha stimulates hepatic fatty acid oxidation to supply substrates that can be metabolized by other tissues.

A simple access pricing rule to achieve the Ramsey outcome for interconnected networks

This paper considers a general and informationally efficient approach to determine the optimal access pricing rule for interconnected networks. It shows that there exists a simple rule that achieves the Ramsey outcome as the unique equilibrium when networks compete in linear prices without network-based price discrimination. The approach is informationally efficient in the sense that the regulator is required to know only the marginal cost structure, i.e. the marginal cost of making and terminating a call. The approach is general in that access prices can depend not only on the marginal costs but also on the retail prices, which can be observed by consumers and therefore by the regulator as well. In particular, I consider the set of linear access pricing rules which includes any fixed access price, the Efficient Component Pricing Rule (ECPR) and the Modified ECPR as special cases. I show that in this set, there is a unique rule that implements the Ramsey outcome as the unique equilibrium independently of the underlying demand conditions.

Entrepreneurial structure of the mercantile company in pre-industrial Catalonia

The mercantile company was the basic form of enterprise in pre-industrial Catalonia. The aim of this paper is to study the formation and development of the mercantile companies in Barcelona whose end was the wholesale and retail sale of textiles in the botigues de teles (textile retail shops) throughout the eighteenth century. These firms were officially registered before a notary and their deeds reveal how these establishments were administered and managed.The study covers a sample of 121 mercantile companies, and the articles and documentation that were put into effect by 32 notaries who were active in Barcelona in the 18th century have been consulted in their entirety. From an initial selection of documentation, a total of 228 deeds registering companies have been found, 107 of which (47%) relate to the creation of companies whose various activities were centred in taverns, textile manufacturing, braiding.... While the 121 companies, which make up our sample and which account for 53% of the deeds registered with the notaries mentioned above, focused exclusively on the management of textile retail shops located in the commercial heart of the city. Thus one point of interest that the documentation reveals is that the majority of the mercantile companies registered by Barcelona notaries throughout the 18th century were establishments which traded in textiles. The first part of the article focuses on the structural characteristics of these enterprises, the number and socio-professional status of the partners and the extent of each partner s involvement in the administration and management. The second part of the article examines the capital investment made by each partner, their rights and obligations agreed on, the sharing out of profits and possible losses and the duration of the companies. The final aim of the paper is to highlight the evolution of these companies through one specific case.

Timing of seasonal sales

We present a model of timing of seasonal sales where stores chooseseveral designs at the beginning of the season without knowingwich one, if any, will be fashionable. Fashionable designs have achance to fetch high prices in fashion markets while non-fashionableones must be sold in a discount market. In the beginning of theseason, stores charge high prices in the hope of capturing theirfashion market. As the end of the season approaches with goods stillon the shelves, stores adjust downward their expectations that theyare carrying a fashionable design, and may have sales to capture thediscount market. Having a greater number of designs induces a storeto put one of them on sales earlier to test the market. Moreover,price competition in the discount market induces stores to startsales earlier because of a greater perceived first-mover advantage incapturing the discount market. More competition, perhaps due todecreases in the cost of product innovation, makes sales occur evenearlier. These results are consistent with the observation that thetrend toward earlier sales since mid-1970's coincides with increasingproduct varieties in fashion good markets and increasing storecompetition.