Loss of heterozygosity of the von Hippel Lindau gene locus in polypoid dysplasia but not flat dysplasia in ulcerative colitis or sporadic adenomas

Carcinoma in ulcerative colitis (UC) develops from dysplastic precursor lesions, which include flat dysplasia (FD) and polypoid dysplasias (PD). PD may present as single or multiple polypoid structures or as plaque-like lesions that, independent of histological grade, are an indication for colectomy. PDs are histologically similar to adenomas and may not be readily distinguished by light microscopy. It is not known whether FD and PD are different entities, or whether they represent etiologically similar lesions with different morphological expression. We microdissected 25 cases of UC with PD and 19 samples of FD with surrounding chronic colitis (CC) in UC. Loss of heterozygosity (LOH) at the von Hippel Lindau (vHL) gene locus and the putative tumor suppressor genes APC, INK4A (9p16), and p53 was studied. LOH of the vHL gene, INK4A (9p16), and APC was also studied in 11 sporadic adenomas of the colon. LOH at the vHL locus was present in 50% of the samples of PD and in 12% of the samples of FD. LOH was seen in CC close to PD and FD in 26% and 12% of cases, respectively. No adenoma showed LOH of the vHL gene markers studied. LOH in p53 was seen in PD in 16% cases and in FD in 42% cases and in CC close to PD and FD in 0% and 14% cases, respectively. LOH patterns between PD and FD of the markers for APC and 9p16 were not different. LOH in APC was seen in two of five cases of adenoma. We conclude that PD and FD share genetic alterations in APC and 9p16 genes. More frequent involvement of the VHL gene in PD and surrounding CC and involvement of p53 in HGD and CC in FD may represent genetic differences between the development of PD and FD and may be the cause of the different morphology. The infrequency of LOH at the vHL locus in adenomas versus PD may serve as a discriminator between adenomas and PD in diagnostically problematic cases.     

Monocular enucleation prevents retinal ganglion-cell loss following neonatal visual cortex damage in cats

Studies were conducted to assess the utility of free solution capillary electrophoresis (CE) for monitoring the effects of selected excipients on the thermal denaturation of a model protein (Ribonuclease A, RNase A) at low pH. Thermal denaturation/unfolding experiments were conducted via temperature-controlled CE using a run buffer of 20 mM citric acid in the pH range of 2.3-3.1, with a marker peptide incorporated to correct for temperature-induced changes in endoosmotic flow. The effects of selected excipients on the thermal unfolding of RNase A were then evaluated by adding either sorbitol, sucrose, polyethylene glycol 400 (PEG 400) or 2-methyl-2,4-pentanediol (MPD) to the electrophoretic run buffer (pH 2.3). Confirmatory denaturation experiments were conducted under the same solution conditions using circular dichroism (CD) spectropolarimetry. Using temperature-controlled CE, an increase in solution pH from 2.3 to 2.7 and 3.1 resulted in an increase in transition temperatures of RNase A by approximately 8 and 13 degrees C, respectively. Similar shifts in transition temperatures were observed when thermal denaturation transitions were monitored by far-UV CD. Sorbitol (0.55-1.1 M) and sucrose (0.55 M) each shifted the denaturation transition temperatures of RNase A to higher values, whereas PEG 400 and MPD had minimal effect on the unfolding transition midpoint at the concentrations evaluated (0.55 M for each). The observed changes in the transition temperatures for RNase A as a function of pH and selected excipients were similar when measured by either CE or far-UV CD. These results support the utility of CE for monitoring the effects of neutral excipients on the thermal denaturation of a model protein under selected conditions. The widespread utility of the technique may be limited by the narrow temperature range of most commercial CE instruments and the need to use extreme pH conditions to monitor the complete denaturation transition.     

Clinical applications of anticancer drugs targeted to topoisomerase II

Agents which 'poison' the enzyme topoisomerase II, have proven to be useful drugs for cancer treatment. Six antineoplastic drugs, which target topoisomerase II (doxorubicin, daunorubicin, idarubicin, mitoxantrone, etoposide and teniposide) are currently approved for clinical use in the United States. In this paper, the strategies and goals of cancer chemotherapy are summarized for the non-clinician. The use, pharmacology and toxicity of each of the six currently approved topoisomerase II inhibiting agents are reviewed.     

Fibular shortening in poliomyelitis

We have determined the nucleotide and encoded amino acid sequences of the capsid, membrane precursor, membrane, envelope, and nonstructural NS1 protein genes of a dengue-2 virus (D2-04) isolated from a patient in Hainan, China. The sequenced region contains a gene organization similar to that of other flaviviruses. The overall amino acid sequence similarity between D2-04 and other dengue-2 viruses is greater than 92%, whereas that between D2-04 and members of the other dengue serotypes is about 65%.     

Development and validation of a Monte Carlo simulation of photon transport in an Anger camera

The geometric component of the point spread function (PSF) of a gamma camera collimator can be determined analytically, and the penetration component can be calculated readily by numerical ray-tracing. A Monte Carlo simulation of photon transport which includes collimator scatter is developed. The simulation was implemented with an array processor which propagates up to 1024 photons in parallel, allowing accurate estimates of the total radial PSF in less than a day. The simulation was tested by imaging monoenergetic point sources of Tc-99m, Cr-51, and Sr-85 (140, 320, and 514 keV, respectively) on a General Electric Star Cam with low-energy, general-purpose, and medium-energy collimators. Comparisons of measured and simulated PSFs demonstrate the validity of the model and the significance of collimator scatter in the degradation of image quality.     

Traumatogenic factors affecting the knees of carpet installers

An ergonomics analysis of carpet installation tasks was performed. The purpose was to identify and quality potential sources of biomechanical trauma that may be responsible for the high rates of knee morbidity found by previous researchers among carpet layers. Nine carpet layers were studied either at an apartment building worksite or at a training school. Results from a job analysis indicated that workers spent approximatately 75% of their time in the kneeling position using a tool called a knee-kicker to stretch and install carpet. Awkward body postures were identified from films of workers installing carpets. At the moment of impact the knee is severely flexed, subtended angles were less than 60 degrees. To obtain measures of impact force on the knee, the kicker-tool was instrumented with a load cell. Workers who executed the hardest kicks with the tool produced impact peak forces that averaged 3019 newtons (N), which is equivalent to about four times body weight. Measures from an accelerometer attached to the worker's knee showed values in ecxess of 120 m/s², which are comparable to those found during vigorous running and jumping exercises. The results imply that repetitive impact of the knee joint from the use of the knee-kicker combined with knee flexion, kneeling and squatting may be responsible for the high level of occupational knee-morbidity found among carpet layers.     

Influence of sources of dietary oils on the life span of stroke-prone spontaneously hypertensive rats

In recent studies, the life span of stroke-prone spontaneously hypertensive (SHRSP) rats was altered by a variety of dietary fats. It was relatively shorter in rats fed canola oil as the sole source of fat. The present study was performed to find out whether the fatty acid profile and the high content of sulfur compounds in canola oil could modulate the life span of SHRSP rats. SHRSP rats (47 d old, n=23/group) were matched by body weight and systolic blood pressure and fed semipurified diets containing 10% canola oil, high-palmitic canola oil, low-sulfur canola oil, soybean oil, high-oleic safflower oil, a fat blend that mimicked the fatty acid composition of canola oil, or a fat blend high in saturated fatty acids. A 1% sodium chloride solution was used as drinking water to induce hypertension. After consuming the diets for 37 d, five rats from each dietary group were killed for collection of blood and tissue samples for biochemical analysis. The 18 remaining animals from each group were used for determining their life span. The mean survival time of SHRSP rats fed canola oil (87.4±4.0 d) was not significantly different (P>0.05) from those fed low-sulfur canola oil (89.7±8.5 d), suggesting that content of sulfur in canola oil has no effect on the life span of SHRSP rats. The SHRSP rats fed the noncanola oil-based diets lived longer (mean survival time difference was 6–13 d, P<0.05) than those fed canola and low-sulfur canola oils. No marked differences in the survival times were observed among the noncanola oil-based groups. The fatty acid composition of the dietary oils and of red blood cells and liver of SHRSP rats killed after 37 d of treatment showed no relationship with the survival times. These results suggest that the fatty acid profile of vegetable oils plays no important role on the life span of SHRSP rat. However, phytosterols in the dietary oils and in liver and brain were inversely correlated with the mean survival times, indicating that the differential effects of vegetable oils might be ascribed, at least partly, to their different phytosterol contents.     

The role ofAzolla in curbing ammonia volatilization from flooded rice systems

By the year 2020, an additional 300 million tons of rice are needed annually to meet the demands of a growing population. If our natural resource base is to be preserved, intensification strategies should rely on integrated nutrient management, making full use of biological nitrogen fixation. TheAzolla-Anabaena complex is amongst the most effective systems of fixing nitrogen. In this paper we present evidence from greenhouse studies on the potential ofAzolla to curb the volatilization of NH₃ following the application of urea to a mixedAzolla-rice culture, providing a new incentive for developing ways of integratingAzolla in intensive rice cultivation systems.The results of a series of short term greenhouse experiments show that a full cover ofAzolla can significantly reduce losses of applied urea-N from 45 and 50% to 20 and 13% for the 30 and 60 kg N ha^–1 treatments, respectively. About one-quarter of the applied N was tied up in theAzolla biomass. The applied N inhibitedAzolla growth as well as the amount of N fixed. Inoculation with smaller quantities ofAzolla allowing for more vigorousAzolla multiplication was equally effective in reducing NH₃ volatilization and doubled the amount of¹⁵N tied-up byAzolla. The reduction in NH₃ volatilization is largely related to the depression byAzolla of the floodwater pH, which in its absence may reach values between 9 and 10 as a result of algal activity.Early rice growth responded positively to urea as well as the large quantities of appliedAzolla and increased the yield potential of the crop. Smaller quantities ofAzolla alone were not effective in this regard. The conservation of fertilizer N byAzolla, particularly when it fully covered the water, was reflected in a synergistic effect on rice dry matter production, amounting to 9% at the 30 kg N rate and 16% at the 60 kg N rate. In all likelihood this interaction is attributable to the higher efficiency of the applied N. The benefits ofAzolla in conserving basal urea-N even in small quantities (200-500 kg fresh material ha^–1), outweighed competition for the applied N and may be as important as its BNF. The most promising integratedAzolla/rice management systems emerging from our studies should be given further attention under field conditions.     

Infrared heated μ-blistering,a new fabrication technology for HARMST

Polymeric replication technologies such as injection moulding or hot-embossing have gained wide acceptance in the microtechnological community, microthermoforming of thin polymer foils, also called μ-blistering, still remains relatively unknown. Although the general potentials of the µ-blistering have already been pointed out, little work has been carried out addressing its capability for high aspect ratio microstructuring. In the scope of this work we therefore demonstrate the feasibility of μ-blistering to obtain aspect ratios for free standing structures of up to 7 within a process cycle time of <4 min. The presented processing technology uniquely combines manufacturing of macro-, micro- and even nanoscopic feature sizes in a single process.     

Designing a supply network artifact for data,process, and people integration

E-procurement and supplier-relationship management systems have helped to substantially advance process execution in supply management. However, current supply network systems still face challenges of high data integration efforts, as well as the decoupling of structured data and processes from the growing amount of digitalized unstructured interactions of supply management professionals. Inspired by the room for improvement posed by this challenges, our research proposes a design for a supply network artifact in supplier qualification that addresses these problems by enabling holistic integration of data, processes, and people. The artifact is developed following an action design research approach. Building on a set of meta-requirements derived from literature and practice explorations, we conceptualize two design principles and derive corresponding design decisions that have been implemented in an software artifact. Finally, we formulate testable hypotheses and evaluate the artifact and its design in the context of supplier qualification. Our results show that the proposed design reduces mental effort of supply management professionals and significantly increases efficiency when performing typical supply network tasks such as supplier qualification.