Class I histone deacetylases 1, 2 and 3 are highly expressed in renal cell cancer

Background Enhanced activity of histone deacetylases (HDAC) is associated with more aggressive tumour behaviour and tumour progression in various solid tumours. The over-expression of these proteins and their known functions in malignant neoplasms has led to the development of HDAC inhibitors (HDI) as new anti-neoplastic drugs. However, little is known about HDAC expression in renal cell cancer. Methods We investigated the expression of HDAC 1, 2 and 3 in 106 renal cell carcinomas and corresponding normal renal tissue by immunohistochemistry on tissue micro arrays and correlated expression data with clinico-pathological parameters including patient survival. Results Almost 60% of renal cell carcinomas expressed the HDAC isoforms 1 and 2. In contrast, HDAC 3 was only detected in 13% of all renal tumours, with particular low expression rates in the clear cell subtype. HDAC 3 was significantly higher expressed in pT1/2 tumours in comparison to pT3/4 tumours. Expression of class I HDAC isoforms correlated with each other and with the proliferative activity of the tumours. We found no prognostic value of the expression of any of the HDAC isoforms in this tumour entity. Conclusion Class I HDAC isoforms 1 and 2 are highly expressed in renal cell cancer, while HDAC 3 shows low, histology dependent expression rates. These unexpected differences in the expression patterns suggests alternative regulatory mechanisms of class I HDACs in renal cell cancer and should be taken into account when trials with isoform selective HDI are being planned. Whether HDAC expression in renal cancers is predictive of responsiveness for HDI will have to be tested in further studies

Remote control of a robotic hand using a leap sensor

This paper presents a low-cost gesture-based remote control of a ro-botic hand. The proposed control architecture is based on a commercial leap motion sensor and an Arduino board, which have been chosen due to their low-cost and user-friendly features. A specific Matlab code has been implemented to collect data from the leap motion sensor and to generate proper instructions to control a robotic hand, which has been 3D print at Sheffield Hallam Univer-sity. Experimental tests have been carried out validate the effectiveness of the proposed remote control for performing various grasping tasks

The FLASHForward Facility at DESY

The FLASHForward project at DESY is a pioneering plasma-wakefield acceleration experiment that aims to produce, in a few centimetres of ionised hydrogen, beams with energy of order GeV that are of quality sufficient to be used in a free-electron laser. The plasma wave will be driven by high-current density electron beams from the FLASH linear accelerator and will explore both external and internal witness-beam injection techniques. The plasma is created by ionising a gas in a gas cell with a multi-TW laser system, which can also be used to provide optical diagnostics of the plasma and electron beams due to the <30 fs synchronisation between the laser and the driving electron beam. The operation parameters of the experiment are discussed, as well as the scientific program.Comment: 19 pages, 9 figure

The Impact of Harvesting and Site Preparation on Stormflow and Water Quality in East Texas

In 1979, nine small forested watersheds were instrumented in East Texas to determine the effect of intensive forest management practices on water quantity and quality. Three replications of three treatments were used: 1) clearcutting - followed by shearing ant windrowing, 2) clearcutting - followed by roller chopping and 3) undisturbed control. Following treatment, the sheared and windrowed sites exposed 57% of the surface soil compared to 16% for the chopped watersheds. During 1981, the first year after treatment, stormflow volumes increased with the intensity of the site disturbance. Sites sheared produced the greatest amount of stormflow (5.76 inches), followed by chopped (3.26 inches) and the undisturbed watersheds (1.03 inches). Stormflow volumes decreased 66% and 57% on the sheared and chopped watersheds the second year following treatment. Stormflow volumes in 1983 were 2.46, 1.75 and 0.84 inches for the sheared, chopped and control watersheds, respectively. Sediment losses were significantly higher on the sheared watersheds (2,620 lb/acre) than the chopped (22 lb/acre), during 1981. By the fall of 1982, the exposure of mineral soil on the sheared sites decreased to 20% and to 4% on the chopped sites. For this reason and the lower volume of runoff, sediment loss for 1982 dropped to 71.3, 4.9 and 4.5 lb/acre for the sheared, chopped and undisturbed watersheds, respectively. Sediment losses in the third year following treatment continued decreasing on the sheared sites (30.9) and remained approximately the same on the chopped and control sites. Nitrate concentrations were significantly different between treatments during 1981: Sheared - 205 ppb, chopped - 96 ppb and control ~ 10 ppb. During 1982, although nitrate concentrations were lower, the sheared watersheds still had a significantly higher concentration. Nitrate concentrations in 1983 remained low at 54, 20 and 10 ppb for the sheared, chopped and control watersheds, respectively. Total nitrogen concentration on the sheared sites was 2,155 ppb, which was significantly higher than the chopped (999 ppb) or the control sites (996 ppb) for 1981. The first year total nitrogen export from the sheared sites (2.79 lb/acre) was 3.5 times greater than the chopped loss (0.76 lb/acre) and 12 times greater than the loss on the control sites (0.24 lb/acre). The second year following treatment, total nitrogen concentrations were not significantly different and total nitrogen loss on the sheared areas was less than half of the loss recorded from the control sites during 1981. Total nitrogen loss in the third year after treatment was reduced to 0.37, 0.20 and 0.08 lb/ acre for the sheared, chopped and control treatments, respectively. Total phosphorus concentrations for 1981 were 221, 85 and 54 ppb for the sheared, chopped and control watersheds, respectively. Total phosphorus loss for this period was only 0.297 lb/acre from the sheared treatments, but was significantly higher than the chopped or undisturbed treatments. A drop in sediment concentrations and runoff in 1982 reduced phosphorus losses on the sheared watersheds by over 90%. Total phosphorus export in 1983 decreased on sheared sites (0.019 lb/acre), but increased slightly on chopped (0.011 lb/acre) and control sites (0.006 lb/acre). Calcium, potassium and sodium concentrations during 1981, were highest for the chopped treatments, while magnesium concentrations were highest on the sheared treatments. Export of these elements was greatest from the sheared sites, except for calcium, which was lost in greater quantities on the chopped sites. During 1982 there was no significant difference between treatments for Ca, Mg, K and Na concentrations. Cation concentrations and losses on the treated watersheds continued declining in the third year following treatment. Increases in stormflow and sediment and nutrient losses appear to be temporary on sheared and chopped treatments. Rapid revegetation established surface cover and reduced mineral soil exposure. As the stabilization of sites continues, treatment differences should diminish. Limiting shearing and windrowing activities to the more gentle slopes will reduce first year erosion and prevent increases in sediment and nutrient losses. Roller chopping on the other hand, appears to cause only minor changes to water yield and quality on slopes of up to 25%

Effect of Forest Site Preparation and Livestock Grazing on Stormflow and Water Quality in the South East

The commercial forestlands of East Texas and Louisiana are the most water-efficient producing areas of the two states. Current and projected water shortages for Texas makes this water-rich area extremely important to future growth and development of Texas. However, little is known about the influence of intensive forest practices or livestock grazing on water quality, yield or site productivity in Texas. This is the only instrumented watershed study in Texas or Louisiana that is currently evaluating the influence of livestock grazing on water and the second study evaluating the impact of intensive forest practices on water. This research is providing information that will enable forest managers, state and federal agencies to select livestock grazing and/or forest management practices that will maintain a productive forest environment and minimize off-site water quality impacts. It is imperative that if Texas in the next 30 years is: 1) to help meet the timber product demand that is projected to be placed on the Southeast, and 2) to meet the projected water shortages we need to understand the impact of intensive forest and livestock grazing practices on site productivity and water. This research is helping provide the basic information needed to manage Southeast forestlands for timber products, red meat and water. The southern states are currently producing half of the nation's wood supply with large demands to increase timber production expected in the next 20 years. The challenge facing forestry in the South is in developing technology and management to meet this increased demand and maintain an acceptable forest environment in the face of increased taxes, rising labor, equipment and energy costs. The intensive forest management practices of harvesting and site preparation have been identified as causing potential declines in site production and as sources of nonpoint pollution. The Clean Water Act (PL 92-500 and PL 95-217) requires identification and control of silvicultural activities and livestock grazing which contribute to nonpoint source pollution. Implementation of "best management practices", either voluntary or mandatory, are the suggested means for maintaining water quality and site productivity. Hydrologic impacts of livestock grazing result primarily from the interactions of climate, vegetation, soil, and intensity and duration of livestock use. Thus, grazing impacts will vary naturally from area to area due to the normal variability of these factors. Few studies have attempted to account for these natural variations. Documentation of the intensity and duration of livestock grazing has been poor or completely ignored in most studies. In East Texas, the impact of livestock grazing on water quality has had no research effort. Most research regarding the impact of grazing upon water quality has been conducted outside the Southern Region and, more importantly, outside of the Gulf Coastal Plains. Because geology, soils , topography, climate, etc. are different, extensions of that research to the East Texas and Louisiana areas may be misleading

Assessment of Stormflow and Water Quality from Undisturbed and Site Prepared Forest Land in East Texas (Final Report)

In 1979, nine small forested watersheds were instrumented in East Texas to determine the effect of intensive forest management practices On water quantity and quality. Three replications of three treatments were used: 1) clearcutting - followed by shearing and windrowing, 2) clearcutting - followed by roller chopping and 3) undisturbed control. Following treatment, the sheared and windrowed sites exposed 57% of the surface soil compared to 16% for the chopped watersheds. During 1981, the first year after treatment, stormflow volumes increased with the intensity of the site disturbance. Sites sheared produced the greatest amount of stormflow (5.76 inches), followed by chopped (3.26 inches) and the undisturbed watersheds (1.03 inches). Stormflow volumes decreased 66% and 57% on the sheared and chopped watersheds the second year following treatment. Sediment losses were significantly higher on the sheared watersheds (2,620 lb/acre) than the chopped (22 lb/acre), during 1981. By the fall of 1982, the exposure of mineral soil on the sheared sites dropped to 20% and to 4% on the chopped sites. For this reason and the lower volume of runoff, sediment loss for 1982 dropped to 71.3, 4.9 and 4.5 lb/acre for the sheared, chopped and undisturbed watersheds, respectively. Nitrate concentrations were significantly different between treatments during 1981: Sheared - 205 ppb, chopped - 96 ppb and control 10 ppb. During 1982, although nitrate concentrations were lower, the sheared watershed still had a significantly higher concentration. Total nitrogen concentration on the sheared sites was 2,155 ppb, which was significantly higher than the chopped (999 ppb) or the control sites (996 ppb) for 1981. The first year total nitrogen export from the sheared sites (2.79 lb/acre) was 3.5 times greater than the chopped loss (0.76 lb/acre) and 12 times greater than the loss on the control sites (0.24 lb/acre). The second year following treatment, total nitrogen concentrations were not significantly different and total nitrogen loss on the sheared areas was less than half of the loss recorded from the control sites during 1981. Total phosphorus concentrations for 1981 were 221, 85 and 54 ppb for the sheared, chopped and control watersheds, respectively. Total phosphorus loss for this period was only 0.297 lb/acre from the sheared treatments, but was significantly higher than the chopped or undisturbed treatments. A drop in sediment concentrations and runoff in 1982 reduced phosphorus losses on the sheared watersheds by over 90%. Calcium, potassium and sodium concentrations during 1981, were highest for the chopped treatments, while magnesium concentrations were highest on the sheared treatments. Export of these elements was greatest from the sheared sites, except for calcium, which was lost in greater quantities on the chopped sites. During 1982 there was no significant difference between treatments for Ca, Mg, K and Na concentrations. The rapid revegetation and reduction in exposed mineral soil that occurred on both sheared and chopped treatments during 1982, resulted in a decrease in runoff and sediment and nutrient losses. As the stabilization of sites continues, treatment differences should diminish. Limiting shearing and windrowing activities to the more gentle slopes will reduce first year erosion and prevent increases in sediment and nutrient losses. Roller chopping on the other hand, appears to cause only minor changes to water yield and quality on slopes of up to 25%

Micro-CT Based Experimental Liver Imaging Using a Nanoparticulate Contrast Agent: A Longitudinal Study in Mice

BACKGROUND: Micro-CT imaging of liver disease in mice relies on high soft tissue contrast to detect small lesions like liver metastases. Purpose of this study was to characterize the localization and time course of contrast enhancement of a nanoparticular alkaline earth metal-based contrast agent (VISCOVER ExiTron nano) developed for small animal liver CT imaging. METHODOLOGY: ExiTron nano 6000 and ExiTron nano 12000, formulated for liver/spleen imaging and angiography, respectively, were intravenously injected in C57BL/6J-mice. The distribution and time course of contrast enhancement were analysed by repeated micro-CT up to 6 months. Finally, mice developing liver metastases after intrasplenic injection of colon carcinoma cells underwent longitudinal micro-CT imaging after a single injection of ExiTron nano. PRINCIPAL FINDINGS: After a single injection of ExiTron nano the contrast of liver and spleen peaked after 4-8 hours, lasted up to several months and was tolerated well by all mice. In addition, strong contrast enhancement of abdominal and mediastinal lymph nodes and the adrenal glands was observed. Within the first two hours after injection, particularly ExiTron nano 12000 provided pronounced contrast for imaging of vascular structures. ExiTron nano facilitated detection of liver metastases and provided sufficient contrast for longitudinal observation of tumor development over weeks. CONCLUSIONS: The nanoparticulate contrast agents ExiTron nano 6000 and 12000 provide strong contrast of the liver, spleen, lymph nodes and adrenal glands up to weeks, hereby allowing longitudinal monitoring of pathological processes of these organs in small animals, with ExiTron nano 12000 being particularly optimized for angiography due to its very high initial vessel contrast

Talin is required for integrin-mediated platelet function in hemostasis and thrombosis

Integrins are critical for hemostasis and thrombosis because they mediate both platelet adhesion and aggregation. Talin is an integrin-binding cytoplasmic adaptor that is a central organizer of focal adhesions, and loss of talin phenocopies integrin deletion in Drosophila. Here, we have examined the role of talin in mammalian integrin function in vivo by selectively disrupting the talin1 gene in mouse platelet precursor megakaryocytes. Talin null megakaryocytes produced circulating platelets that exhibited normal morphology yet manifested profoundly impaired hemostatic function. Specifically, platelet-specific deletion of talin1 led to spontaneous hemorrhage and pathological bleeding. Ex vivo and in vitro studies revealed that loss of talin1 resulted in dramatically impaired integrin αIIbβ3-mediated platelet aggregation and β1 integrin–mediated platelet adhesion. Furthermore, loss of talin1 strongly inhibited the activation of platelet β1 and β3 integrins in response to platelet agonists. These data establish that platelet talin plays a crucial role in hemostasis and provide the first proof that talin is required for the activation and function of mammalian α2β1 and αIIbβ3 integrins in vivo