Direct visualization of the putative portal in the Kaposi's sarcoma-associated herpesvirus capsid by cryoelectron tomography.

Genetic and biochemical studies have suggested the existence of a bacteriophage-like, DNA-packaging/ejecting portal complex in herpesviruses capsids, but its arrangement remained unknown. Here, we report the first visualization of a unique vertex in the Kaposi's sarcoma-associated herpesvirus (KSHV) capsid by cryoelectron tomography, thus providing direct structural evidence for the existence of a portal complex in a gammaherpesvirus. This putative KSHV portal is an internally localized, umbilicated structure and lacks all of the external machineries characteristic of portals in DNA bacteriophages.

Dominance of the proximal coordinate frame in determining the locations of hippocampal place cell activity during navigation.

The place-specific activity of hippocampal cells provides downstream structures with information regarding an animal's position within an environment and, perhaps, the location of goals within that environment. In rodents, recent research has suggested that distal cues primarily set the orientation of the spatial representation, whereas the boundaries of the behavioral apparatus determine the locations of place activity. The current study was designed to address possible biases in some previous research that may have minimized the likelihood of observing place activity bound to distal cues. Hippocampal single-unit activity was recorded from six freely moving rats as they were trained to perform a tone-initiated place-preference task on an open-field platform. To investigate whether place activity was bound to the room- or platform-based coordinate frame (or both), the platform was translated within the room at an "early" and at a "late" phase of task acquisition (Shift 1 and Shift 2). At both time points, CA1 and CA3 place cells demonstrated room-associated and/or platform-associated activity, or remapped in response to the platform shift. Shift 1 revealed place activity that reflected an interaction between a dominant platform-based (proximal) coordinate frame and a weaker room-based (distal) frame because many CA1 and CA3 place fields shifted to a location intermediate to the two reference frames. Shift 2 resulted in place activity that became more strongly bound to either the platform- or room-based coordinate frame, suggesting the emergence of two independent spatial frames of reference (with many more cells participating in platform-based than in room-based representations).

Development of automated image analysis tools for verification of radiotherapy field accuracy with an electronic portal imaging device

The successful management of cancer with radiation relies on the accurate deposition of a prescribed dose to a prescribed anatomical volume within the patient. Treatment set-up errors are inevitable because the alignment of field shaping devices with the patient must be repeated daily up to eighty times during the course of a fractionated radiotherapy treatment. With the invention of electronic portal imaging devices (EPIDs), patient's portal images can be visualized daily in real-time after only a small fraction of the radiation dose has been delivered to each treatment field. However, the accuracy of human visual evaluation of low-contrast portal images has been found to be inadequate. The goal of this research is to develop automated image analysis tools to detect both treatment field shape errors and patient anatomy placement errors with an EPID. A moments method has been developed to align treatment field images to compensate for lack of repositioning precision of the image detector. A figure of merit has also been established to verify the shape and rotation of the treatment fields. Following proper alignment of treatment field boundaries, a cross-correlation method has been developed to detect shifts of the patient's anatomy relative to the treatment field boundary. Phantom studies showed that the moments method aligned the radiation fields to within 0.5mm of translation and 0.5$\sp\circ$ of rotation and that the cross-correlation method aligned anatomical structures inside the radiation field to within 1 mm of translation and 1$\sp\circ$ of rotation. A new procedure of generating and using digitally reconstructed radiographs (DRRs) at megavoltage energies as reference images was also investigated. The procedure allowed a direct comparison between a designed treatment portal and the actual patient setup positions detected by an EPID. Phantom studies confirmed the feasibility of the methodology. Both the moments method and the cross-correlation technique were implemented within an experimental radiotherapy picture archival and communication system (RT-PACS) and were used clinically to evaluate the setup variability of two groups of cancer patients treated with and without an alpha-cradle immobilization aid. The tools developed in this project have proven to be very effective and have played an important role in detecting patient alignment errors and field-shape errors in treatment fields formed by a multileaf collimator (MLC). ^

Portal vein omentin is increased in patients with liver cirrhosis but is not associated with complications of portal hypertension

BACKGROUND: Omentin is a visceral fat-derived adipokine associated with endothelium-dependent vasodilation. Impaired endothelial function is a major cause of portal hypertension in liver cirrhosis. The aim was to assess associations of omentin with systemic markers of endothelial function, namely arginine and asymmetric dimethylarginine (ADMA) and complications of portal hypertension in liver cirrhosis. MATERIALS AND METHODS: Systemic omentin was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS) and hepatic venous serum (HVS) of 40 patients with liver cirrhosis and 10 liver-healthy controls. ADMA and arginine were determined in SVS of the patients by ELISA. RESULTS: Omentin is elevated in PVS and tends to be increased in SVS and HVS of patients with liver cirrhosis compared with controls. Omentin is principally expressed in visceral fat, and PVS omentin tends to be higher than SVS levels. Lower HVS than PVS omentin suggests that omentin may be partly removed from the circulation by the liver. Omentin in serum is not associated with stages of liver cirrhosis defined by CHILD-POUGH or MELD score and is not affected in patients with ascites. HVS omentin tends to be reduced in patients with large varices compared with patients without/with small varices. Arginine/ADMA ratio is reduced in patients with massive ascites but is not associated with variceal size. Further, Arginine/ADMA ratio does not correlate with omentin. CONCLUSION: Current data show that PVS omentin is increased in liver cirrhosis but is not associated with complications of portal hypertension

Still frame from the hour of death: Acute intracerebral hemorrhage on post-mortem computed tomography in a decomposed corpse

We report a case of an acute hypertensive, intracerebral hemorrhage on post-mortem computed tomography (PMCT) in a decomposed corpse. In clinical radiology, the appearance of blood on cross-sectional imaging is used to estimate the age of intracranial hemorrhage. The findings from this case indicate that characteristics of intracerebral blood on PMCT provide a still frame of the hemorrhage, as it was at the time of death. This observation suggests that the appearance of blood on PMCT may be used to estimate the age of an intracerebral hemorrhage but not to estimate the post-mortem interval.

Effect of meal ingestion on liver stiffness in patients with cirrhosis and portal hypertension.

BACKGROUND AND AIMS Liver stiffness is increasingly used in the non-invasive evaluation of chronic liver diseases. Liver stiffness correlates with hepatic venous pressure gradient (HVPG) in patients with cirrhosis and holds prognostic value in this population. Hence, accuracy in its measurement is needed. Several factors independent of fibrosis influence liver stiffness, but there is insufficient information on whether meal ingestion modifies liver stiffness in cirrhosis. We investigated the changes in liver stiffness occurring after the ingestion of a liquid standard test meal in this population. METHODS In 19 patients with cirrhosis and esophageal varices (9 alcoholic, 9 HCV-related, 1 NASH; Child score 6.9±1.8), liver stiffness (transient elastography), portal blood flow (PBF) and hepatic artery blood flow (HABF) (Doppler-Ultrasound) were measured before and 30 minutes after receiving a standard mixed liquid meal. In 10 the HVPG changes were also measured. RESULTS Post-prandial hyperemia was accompanied by a marked increase in liver stiffness (+27±33%; p<0.0001). Changes in liver stiffness did not correlate with PBF changes, but directly correlated with HABF changes (r = 0.658; p = 0.002). After the meal, those patients showing a decrease in HABF (n = 13) had a less marked increase of liver stiffness as compared to patients in whom HABF increased (n = 6; +12±21% vs. +62±29%,p<0.0001). As expected, post-prandial hyperemia was associated with an increase in HVPG (n = 10; +26±13%, p = 0.003), but changes in liver stiffness did not correlate with HVPG changes. CONCLUSIONS Liver stiffness increases markedly after a liquid test meal in patients with cirrhosis, suggesting that its measurement should be performed in standardized fasting conditions. The hepatic artery buffer response appears an important factor modulating postprandial changes of liver stiffness. The post-prandial increase in HVPG cannot be predicted by changes in liver stiffness.

Contribution of Starlette, Stella, and AJISAI to the SLR-derived global reference frame

The contribution of Starlette, Stella, and AJI-SAI is currently neglected when defining the International Terrestrial Reference Frame, despite a long time series of precise SLR observations and a huge amount of available data. The inferior accuracy of the orbits of low orbiting geodetic satellites is the main reason for this neglect. The Analysis Centers of the International Laser Ranging Service (ILRS ACs) do, however, consider including low orbiting geodetic satellites for deriving the standard ILRS products based on LAGEOS and Etalon satellites, instead of the sparsely observed, and thus, virtually negligible Etalons. We process ten years of SLR observations to Starlette, Stella, AJISAI, and LAGEOS and we assess the impact of these Low Earth Orbiting (LEO) SLR satellites on the SLR-derived parameters. We study different orbit parameterizations, in particular different arc lengths and the impact of pseudo-stochastic pulses and dynamical orbit parameters on the quality of the solutions. We found that the repeatability of the East and North components of station coordinates, the quality of polar coordinates, and the scale estimates of the reference are improved when combining LAGEOS with low orbiting SLR satellites. In the multi-SLR solutions, the scale and the Z component of geocenter coordinates are less affected by deficiencies in solar radiation pressure modeling than in the LAGEOS-1/2 solutions, due to substantially reduced correlations between the Z geocenter coordinate and empirical orbit parameters. Eventually, we found that the standard values of Center-of-mass corrections (CoM) for geodetic LEO satellites are not valid for the currently operating SLR systems. The variations of station-dependent differential range biases reach 52 and 25 mm for AJISAI and Starlette/Stella, respectively, which is why estimating station dependent range biases or using station-dependent CoM, instead of one value for all SLR stations, is strongly recommended.This clearly indicates that the ILRS effort to produce CoM corrections for each satellite, which are site-specific and depend on the system characteristics at the time of tracking,is very important and needs to be implemented in the SLR data analysis.

Elevated liver regeneration in response to pharmacological reduction of elevated portal venous pressure by terlipressin after partial hepatectomy.

BACKGROUND Liver regeneration is of crucial importance for patients undergoing living liver transplantations or extended liver resections and can be associated with elevated portal venous pressure, impaired hepatic regeneration, and postoperative morbidity. The aim of this study was to assess whether reduction of portal venous pressure by terlipressin improves postoperative liver regeneration in normal and steatotic livers after partial hepatectomy in a rodent model. METHODS Portal venous pressure was assessed after minor (30%), standard (60%), or extended (80%) partial hepatectomy (PH) in mice with and without liver steatosis. Liver regeneration was assessed by BrdU incorporation and Ki-67 immunostaining. RESULTS Portal venous pressure was significantly elevated post-PH in mice with normal and steatotic livers compared to sham-operated mice. Reduction of elevated portal pressure after 80% PH by terlipressin was associated with an increase of hepatocellular proliferation. In steatotic livers, animals treated with terlipressin had an increase in liver regeneration after 30% PH and increased survival after 60% PH. Mechanistically, terlipressin alleviated IL-6 mRNA expression following PH and down-regulated p21 and GADD45 mRNA suggesting a reduction of cell cycle inhibition and cellular stress. CONCLUSIONS Reduction of elevated portal pressure post-PH by the use of terlipressin improves liver regeneration after PH in lean and steatotic mouse livers.

Disastrous Portal Vein Embolization Turned into a Successful Intervention

Portal vein embolization (PVE) may be performed before hemihepatectomy to increase the volume of future liver remnant (FLR) and to reduce the risk of postoperative liver insufficiency. We report the case of a 71-year-old patient with hilar cholangiocarcinoma undergoing PVE with access from the right portal vein using a mixture of n-butyl-2-cyanoacrylate and ethiodized oil. During the procedure, nontarget embolization of the left portal vein occurred. An aspiration maneuver of the polymerized plug failed; however, the embolus obstructing portal venous flow in the FLR was successfully relocated into the right portal vein while carefully bypassing the plug with a balloon catheter, inflating the balloon, and pulling the plug into the main right portal vein.

How parties frame social citizenship and the inclusion of immigrants in Germany, Switzerland and the United Kingdom

Recent research on the transformation of West European party systems emphasises that cultural issues such as immigration have gained in importance besides the traditional socio-economic cleavage. While this literature shows that parties address not only cultural but also economic is-sues, it has paid less attention on whether parties combine cultural and economic issues. In this paper we focus on immigrants’ social rights by analysing if and how mainstream parties combine immigration and redistributive issues. Drawing on Faist (1995), we distinguish three different perspectives how political actors, here mainstream parties, might react to the welfare chauvinist claims that aim to restrict immigrants’ social rights. Our analysis relies on party manifestos in Germany, Switzerland and the United Kingdom between 1999 and 2011. The results of the anal-ysis indicate that variation is found among party families, in particular among the left. Even though the purpose of the paper is not to ‘prove’ that the populist challenge explains how the mainstream left-wing parties behave, the results allow nonetheless for interpreting mainstream parties’ strategic combination of welfare and immigration issues as a response to anti-immigration and anti-integration issues raised by populist challengers.

Investigating policy processes: The Governance Analytical Frame-work (GAF)

Societies develop ways of making decisions regarding collective problems, thereby creating norms, rules, and institutions; this is what governance is about. In policy research, governance has become an important focus of attention; but debates show a lack of clarity at the conceptual level and a confusion between the use of the concept for prescriptive and analytical purposes. The present article is based on the hypothesis that using a clarified, non-normative governance perspective in policy research can contribute to an improved understanding of political processes, including formal and unrecognised ones, those embedded in larger and smaller social systems, as well as both vertical and horizontal political arrangements. The paper is the result of a collaborative engagement with the concept of governance within several networks, leading to the development of the Governance Analytical Framework (GAF). The GAF is a practical methodology for investigating governance processes, based on five analytical tools: problems, actors, social norms, processes, and nodal points. Besides describing the conceptual sources and analytical purpose of these five tools, the paper presents examples of how the GAF can be operationalised.