Search

Nonselective inhibitors of human histone deacetylases (HDAC) are known to have antitumor activity in mice in vivo, and several of them are under clinical investigation. The first of these, Vorinostat (SAHA), has been approved for treatment of cutaneous T-cell lymphoma. Questions remain concerning which HDAC isotype(s) are the best to target for anticancer activity and whether increased efficacy and safety will result with an isotype-selective HDAC inhibitor. We have developed an isotype-selective HDAC inhibitor, MGCD0103, which potently targets human HDAC1 but also has inhibitory activity against HDAC2, HDAC3, and HDAC11 in vitro. In intact cells, MGCD0103 inhibited only a fraction of the total HDAC activity and showed long-lasting inhibitory activity even upon drug removal. MGCD0103 induced hyperacetylation of histones, selectively induced apoptosis, and caused cell cycle blockade in various human cancer cell lines in a dose-dependent manner. MGCD0103 exhibited potent and selective antiproliferative activities against a broad spectrum of human cancer cell lines in vitro, and HDAC inhibitory activity was required for these effects. In vivo, MGCD0103 significantly inhibited growth of human tumor xenografts in nude mice in a dose-dependent manner and the antitumor activity correlated with induction of histone acetylation in tumors. Our findings suggest that the isotype-selective HDAC inhibition by MGCD0103 is sufficient for antitumor activity in vivo and that further clinical investigation is warranted. [Mol Cancer Ther 2008;7(4):759–68]

Supplementary Table 1 from MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo

Supplementary Table 2 from MGCD0103, a novel isotype-selective histone deacetylase inhibitor, has broad spectrum antitumor activity in vitro and in vivo

Using nationwide survey data, we investigate U.S. meat goat producer preferences and willingness to pay for meat goat breeding stock attributes. Discrete choice experiments were employed, and mixed logit and latent class models were used for analysis. Results showed that producers preferred animals that were highly masculine/feminine, had good structure and soundness, and were of the Boer breed, whereas they preferred fewer animals that were older, of Kiko and Spanish breeds, and priced higher. Significant preference heterogeneity was found among the respondents. Larger-scale producers had greater preference for high masculinity/femininity, good structure and soundness, and Boer bucks.

This study determines i) scale and technical efficiencies, ii) marginal productive contributions for inputs and outputs and iii) efficiency drivers of meat goat farms in the USA. We estimate an input distance function (IDF) using a stochastic production frontier (SPF) technique. The average technical efficiency (TE) for the USA meat goat whole farm was 0.74. The operator education level, percentage of annual net farm income from the goat operation, regional differences and holding of an off farm job are the efficiency drivers of USA meat goat farms. We find increasing returns to scale (RTS) for USA meat goat farms. Our results suggest that USA meat goat farms can be scale efficient if their optimal size of operation is greater than approximately 64 goats or greater than 40 breeding does. Empirical Monte Carlo (MC) simulation techniques show the consistency of finite-sample properties for the input distance function.

Meat goat producers were queried to determine subjective estimates of premiums they would receive for slaughter kids of various selection classes. Market-based predicted premium estimates were obtained via regression using published U.S. Department of Agriculture Agricultural Marketing Service data. Subjective versus market-based predicted premium estimates were compared to determine producer accuracy in predicting premiums. Producers tended to overestimate quality premiums. Producers more accurate in their estimates tended to be larger-scale and older and to hold college degrees, sell more slaughter goats via auction, and manage their goats more intensively. Results contribute to the literature on producer accuracy in predicting prices.

Pasture systems for grass-fed beef production in the Gulf Coast region were evaluated for profitability and sustainability over the period 2009/2010 to 2011/2012. May-weaned steers were divided into groups and randomly placed into different pasture systems. Data on input usage, output quantities, and carbon emissions were recorded and analyzed. The least complex grazing system yielded higher profit than the most complex, but the most complex produced the lowest greenhouse gas impact. A trade-off was found between profitability and greenhouse gas impact among the systems.

Wide band gap (WBG) semiconductor devices have demonstrated superior electrical and thermal performance, compared to their silicon-based counterparts. However, innovative power module packaging design and materials suitable to WBG devices are required. In this paper, the development of a new high power density module using the Power Overlay (POL) packaging platform is presented. The wirebond-less packaging platform has shown significantly reduced electrical parasitics, while providing a thin profile to allow double-side cooling and the integration of gate drive circuits. Thermal cycling and high temperature storage tests were conducted on specimens fabricated and assembled by production equipment. The results presented here were used to establish design guidelines for reliable operation of POL-based power modules.

Costs and returns of pasture-based dairy production are compared with those of conventional production using matching samples. Both whole-farm and dairy enterprise-level estimates are made using the U.S. Department of Agriculture's Agricultural Resource Management Survey data. Conventional farms are matched to pasture-based farms on the basis of operation scale, scope, region, and farmer demographics and adoption of technology. Results show for pasture-based production lower net farm income on per-cow, per-hundredweight milk produced, and total bases. On an enterprise basis, results show for pasture-based production, higher net return over operating cost and lower net return over total cost per hundredweight milk produced.

The present research examines the effect of stocking method, i.e., continuous and rotational, and set (fixed) stocking rate on labor requirements, costs, and profits in cow-calf beef production. Two replicates of 4 adjacent pastures each, containing a mixed warm-season, perennial grass sod [common bermudagrass, Cynodon dactylon (L.) Pers.; dallisgrass, Paspalum dilatatum Poir.], were overseeded to ‘Marshall’ annual ryegrass [Lolium multiflorum (Lam.)] in the autumn of 2 consecutive years. Within each replicate of 4 pastures, one of the following grazing treatments was randomly assigned each pasture: rotationally stocked (8 paddocks) at a low, medium, or high stocking rate (RL, RM, and RH) and continuously stocked at a moderate stocking rate (CM). Labor activities, expenditures, sales, and equipment usages were recorded throughout the study. On a per-cow basis, total labor usage declined (P 0.90) and would not justify the additional labor associated with rotational grazing management.

Louisiana State University Agricultural Center cost estimates for single-crop crawfish production costs are analyzed for the period, 1991–2010, to determine changes in the cost components of Louisiana crawfish production. Fuel costs have contributed the most and fixed expenses the least to increased production costs, with total expenses per acre increasing by an average of 3.8% per year if land is not included and by 3.6% per year if land is included. Crawfish prices have varied greatly over the period, ranging from $0.50/lb in 1993 to $1.75/lb in 2000. Production practices used by Louisiana crawfish producers are highly variable, creating challenges for estimating representative production cost estimates.

The organization of the Baton Rouge, Louisiana, retail food industry was analyzed to determine whether spatial competition influenced the cost and availability of food items. Using a spatial competition gravity variable, the costs of two separate market baskets were analyzed in January 2009, and the factors influencing spatial competition were determined. Store type (chain or supercenter) was found to be the most significant determinant of food costs, validating findings of past studies. Although food was not found to be more expensive in low-income areas, results suggest that residents in low-income and rural areas have disincentives to purchase affordable, available healthy food due to the spatial organization of their local food market.

The U.S. dairy industry is undergoing rapid structural change, evolving from a structure including many small farmers in the Upper Midwest and Northeast to one that includes very large farms in new production regions. Small farms are struggling to retain competitiveness via improved management and low-input systems. Using data from USDA’s Agricultural Resource Management Survey, we determine the extent of U.S. conventional and pasture-based milk production during 2003-2007, and estimate net returns, scale efficiency, and technical efficiency associated with the systems across different operation sizes. We compare the financial performance of small conventional and pasture-based producers with one another and with largescale producers. A stochastic production frontier is used to analyze performance over the period for conventional and pasture technologies identified using a binomial logit model. Large conventional farms generally outperformed smaller farms using most economic measures – technical efficiency, various profitability measures, and returns to scale.

This study addresses the influence of location of a media-reported beef safety problem on consumer perceptions of the safety of their local beef supplies. A mail survey (the research instrument) was sent to 2,500 households in five major U.S. cities. The impacts of location and household socioeconomic characteristics on consumer perceptions of the applicability of a nationally reported safety infraction in one area to the safety of beef in the consumers' local food service market are discussed. The results indicate that the hospitality industry, especially firms with outlets located throughout the United States, should inform customers of the source of beef served in each outlet.

The U.S. ostrich industry was introduced in the 1980s and experienced rapid expansion in the late 1980s and early 1990s. Breeding stock prices rose rapidly and subsequently plummeted during 1993–1995. High prices are to be expected in the introductory stage of an industry. However, the magnitude of prices in the ostrich industry is likely due to overestimates of ostrich productivity and future demand for ostrich products, as well as speculation in the ostrich market. This paper discusses the evolution of the industry from the mid-1980s to the present. Copyright 2002, Oxford University Press.

Velogenic viscerotropic Newcastle disease (vvNCD), which is endemic in Cambodia, can be prevented in theory by a combination of biosecurity and immunization of broiler flocks. The relative contribution of appropriate biosecurity and effective vaccination was quantified at the farm level, applying realistic projections for capital investment, fixed and variable production costs and losses following infection. Non-protected broiler flocks generate a loss when the probability of vvNCD infection exceeds 0.4. Applying both biosecurity and effective vaccination would sustain profitability up to a probability of exposure of 1.0. The benefit to cost ratios for alternative strategies were evaluated for a range of probabilities of exposure to vvNCD extending from 0.1 to 1.0. The benefit-to-cost ratio for biosecurity exceeded unity at a risk of exposure exceeding 0.1, and 0.2 for vaccination and the combination of vaccination and biosecurity respectively. A sensitivity analysis demonstrated that the efficiency of protection, feed cost, and financial consequences of infection markedly affected the projected benefit-to-cost ratios associated with alternative methods of prevention.

Due to pending legislation worldwide, the semiconductor packaging industry is switching over to Pb-free electronics assembly. Flip chip packaging, which is one of the fastest growing segments of packaging technology, is also affected by this trend. It is a common practice to underfill flip chip devices to compensate for the coefficient of thermal expansion (CTE) mismatch between the die and the chip carrier. However, compatible underfill materials and processes are necessary for the effective migration of flip chip packaging towards Pb-free. Among the various underfilling techniques used in the industry, the no-flow underfill (NFU) process has the potential to increase throughput and reduce manufacturing costs as stated in D. Gamota and C. Melton (1998). There has been a significant research effort within the industry to develop NFU materials and processes for eutectic applications, but Pb-free reflow temperatures pose a significant challenge to the development of a NFU that is compatible with the Pb-free assembly process. Recently, we have developed a Pb-free compatible NFU material with a combination of self fluxing capability and cure kinetics that allows for successful assembly of 95.5Sn/3.8Ag/0.7Cu bumped flip chip devices. In this paper, the effect of various process variables that affect voiding in the underfill interface is investigated. In addition to these studies, the assembly yields for a Pb-free compatible underfill used to assemble different flip chip components with 95.5Sn/3.8Ag/0.7Cu alloy are discussed

Flip chip packaging is one of the fastest growing segments in electronics packaging technology. The semiconductor packaging industry is continuing to migrate towards Pb-free electronics assembly. Therefore, the development of compatible materials for Pb-free flip chip packaging is critical to this transition [1]. Flip chip devices are commonly underfilled to compensate for the mismatch in the Coefficient of Thermal Expansion (CTE) between the die and the chip carrier. The No Flow Underfill (NFU) process is a type that can increase the throughput of the flip chip assembly process and reduce manufacturing costs. Significant research has been performed to develop NFUs for eutectic applications. However, further research is required for the development of NFUs that are compatible with the Pb-free solders and the high temperature reflow process associated with these solders. In this paper, the challenges associated with the development of 'filled' underfill formulations for assembly with the 95.5Sn/3.8Ag/0.7Cu bumped flip chip devices are discussed. The effects of process variables that affect voiding in the underfill layer have been presented. The impact on voiding due to stencil printing of the underfill has been discussed. The impact on assembly reliability due to the underfill material properties has also been reported.Copyright © 2006 by General Motors Corporation

The assembly and packaging of electronic devices today is becoming increasingly challenging and demanding because of requirements for smaller, faster and lighter products that provide increasing functionality at low cost. These requirements continue to place greater demands on the electronics industry and mandate improved packaging technology. In part, flip chip packaging technology is the response to these demands and provides a solution to these challenges. While flip chip packaging provides a solution to evolving device requirements, underfill materials are required to improve flip chip device reliability. These resins overcome poor device reliability issues resulting from the mismatch of coefficient of thermal expansion (CTE) between the silicon die and the organic substrate. However, offsetting the gains in device reliability are additional processing steps that adversely affect manufacturing productivity. To compensate for this adverse effect on manufacturing productivity, several new processes, such as wafer level underfill, have been developed. In this paper, we describe the assembly and reliability of flip chips with a nanofilled wafer level underfill (WLU). This approach allows application of the underfill material on the entire wafer, such that many chips can be underfilled simultaneously. Assembly is then carried out with a compatible epoxy flux material. Air-to-air thermal shock (AATS) results and failure mechanisms are described for this novel approach