Slit2 prevents neutrophil recruitment and renal ischemia-reperfusion injury.

Neutrophils recruited to the postischemic kidney contribute to the pathogenesis of ischemia-reperfusion injury (IRI), which is the most common cause of renal failure among hospitalized patients. The Slit family of secreted proteins inhibits chemotaxis of leukocytes by preventing activation of Rho-family GTPases, suggesting that members of this family might modulate the recruitment of neutrophils and the resulting IRI. Here, in static and microfluidic shear assays, Slit2 inhibited multiple steps required for the infiltration of neutrophils into tissue. Specifically, Slit2 blocked the capture and firm adhesion of human neutrophils to inflamed vascular endothelial barriers as well as their subsequent transmigration. To examine whether these observations were relevant to renal IRI, we administered Slit2 to mice before bilateral clamping of the renal pedicles. Assessed at 18 hours after reperfusion, Slit2 significantly inhibited renal tubular necrosis, neutrophil and macrophage infiltration, and rise in plasma creatinine. In vitro, Slit2 did not impair the protective functions of neutrophils, including phagocytosis and superoxide production, and did not inhibit neutrophils from killing the extracellular pathogen Staphylococcus aureus. In vivo, administration of Slit2 did not attenuate neutrophil recruitment or bacterial clearance in mice with ascending Escherichia coli urinary tract infections and did not increase the bacterial load in the livers of mice infected with the intracellular pathogen Listeria monocytogenes. Collectively, these results suggest that Slit2 may hold promise as a strategy to combat renal IRI without compromising the protective innate immune response.

Time-variable gravity signal in Greenland revealed by high-low satellite-to-satellite tracking

[1] In the event of a termination of the Gravity Recovery and Climate Experiment (GRACE) mission before the launch of GRACE Follow-On (due for launch in 2017), high-low satellite-to-satellite tracking (hl-SST) will be the only dedicated observing system with global coverage available to measure the time-variable gravity field (TVG) on a monthly or even shorter time scale. Until recently, hl-SST TVG observations were of poor quality and hardly improved the performance of Satellite Laser Ranging observations. To date, they have been of only very limited usefulness to geophysical or environmental investigations. In this paper, we apply a thorough reprocessing strategy and a dedicated Kalman filter to Challenging Minisatellite Payload (CHAMP) data to demonstrate that it is possible to derive the very long-wavelength TVG features down to spatial scales of approximately 2000 km at the annual frequency and for multi-year trends. The results are validated against GRACE data and surface height changes from long-term GPS ground stations in Greenland. We find that the quality of the CHAMP solutions is sufficient to derive long-term trends and annual amplitudes of mass change over Greenland. We conclude that hl-SST is a viable source of information for TVG and can serve to some extent to bridge a possible gap between the end-of-life of GRACE and the availability of GRACE Follow-On.

Earth gravity field recovery using GPS, GLONASS, and SLR satellites

The time variable Earth’s gravity field provides the information about mass transport within the system Earth, i.e., the relationship of mass transport between atmosphere, oceans, and land hydrology. We recover the low-degree parameters of the time variable gravity field using microwave observations from GPS and GLONASS satellites and from SLR data to five geodetic satellites, namely LAGEOS-1/2, Starlette, Stella, and AJISAI. GPS satellites are particularly sensitive to specific coefficients of the Earth's gravity field, because of the deep 2:1 orbital resonance with Earth rotation (two revolutions of the GPS satellites per sidereal day). The resonant coefficients cause, among other, a “secular” drift (actually periodic variations of very long periods) of the semi-major axes of up to 5.3 m/day of GPS satellites. We processed 10 years of GPS and GLONASS data using the standard orbit models from the Center of Orbit Determination in Europe (CODE) with a simultaneous estimation of the Earth gravity field coefficients and other parameters, e.g., satellite orbit parameters, station coordinates, Earth rotation parameters, troposphere delays, etc. The weekly GNSS gravity solutions up to degree and order 4/4 are compared to the weekly SLR gravity field solutions. The SLR-derived geopotential coefficients are compared to monthly GRACE and CHAMP results.

Cortisol levels and history of depression in acute coronary syndrome patients

BACKGROUND: Depressed mood following an acute coronary syndrome (ACS) is a risk factor for future cardiac morbidity. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation is associated with depression, and may be a process through which depressive symptoms influence later cardiac health. Additionally, a history of depression predicts depressive symptoms in the weeks following ACS. The purpose of this study was to determine whether a history of depression and/or current depression are associated with the HPA axis dysregulation following ACS. METHOD: A total of 152 cardiac patients completed a structured diagnostic interview, a standardized depression questionnaire and a cortisol profile over the day, 3 weeks after an ACS. Cortisol was analysed using: the cortisol awakening response (CAR), total cortisol output estimated using the area under the curve method, and the slope of cortisol decline over the day. RESULTS: Total cortisol output was positively associated with history of depression, after adjustment for age, gender, marital status, ethnicity, smoking status, body mass index (BMI), Global Registry of Acute Cardiac Events (GRACE) risk score, days in hospital, medication with statins and antiplatelet compounds, and current depression score. Men with clinically diagnosed depression after ACS showed a blunted CAR, but the CAR was not related to a history of depression. CONCLUSIONS: Patients with a history of depression showed increased total cortisol output, but this is unlikely to be responsible for associations between depression after ACS and later cardiac morbidity. However, the blunted CAR in patients with severe depression following ACS indicates that HPA dysregulation is present.

Die Sakralisierung des Alpenraums: Kulturelle Interpretationsmuster der rätischen Kapuzinermission (17. und 18. Jh.)

The Capuchins of the Rhaetic Missions had to deal with local forms of catholic piety, which for them were almost as exotic as the religious practices of non-Christian communities in Asia or America. Therefore they regarded it as their task to propagate the true faith among the “schismatic” Catholics from the Grisons. For this purpose, the Capuchins developed a particular pattern of interpretation: They created a sacred territory in which the divine grace can be experienced by the faithful. Hence the missionaries built new churches and chapels, decorated the old ones in baroque style and brought numerous of holy relics from Italy. Thus, they enforced the sacralisation of the alpine space. Recent developments in cultural studies and social sciences make it possible to capture such processes of spacing more precisely. In the course of the “spatial turn”, space is no longer conceived as a physical entity but now is regarded as a human construct. The paper discusses possibilities and limitations of “space” as an analytical category for the study of mission within Catholicism. The sociological concept of space developed by Martina Löw (2001) is used as starting point. This allows the simultaneous consideration of social interactions and cultural contexts in construction of “sacred space”.

Wieczna kobiecość i emancypacja kobiet: obraz kobiecości w twórczości Karoliny Světlej

To nie przypadek, że wyrażenie „wieczna kobiecość" ukute przez Goethego zbiega się w czasie z pierwszymi zachodnimi próbami emancypacji kobiet. W chwili, kiedy model kobiety istniejącej tylko w zależności od mężczyzny zaczyna być kwestionowany, kategoria wiecznej kobiecości pozwala ponownie potwierdzić ten model, wypełniając go pozytywnymi wartościami. Naturą kobiety jest być uległą i oddaną, a te cechy sprawiają, że kobieta jest depozytariuszem wszelkiej potencjalnej zbawczej łaski. Tak w Fauście Goethego, przypada Małgorzacie, dziewczynie naiwniej, niewinnej, niewykształconej i bez własnej woli, wykupić Fausta siłą swojej miłości. Wszystko dzieje się tak, jakby pozytywna kodyfikacja właściwości kobiet dzięki kategorii wiecznej kobiecości służyła tylko lepszemu ukryciu rzeczywistości ich ucisku; feministki jednak nie dają się zwieść: ideały popierane przez kategorię wiecznej kobiecości są a priori niezgodne z emancypacją kobiet. Karolina Světlá, jedna z najważniejszych postaci w walce o zrównanie praw między mężczyznami i kobietami w Czechach w XIX wieku, wykorzystywała przecież intensywnie w swojej literackiej twórczości ten model kobiety, która poświęca się dla kochanego mężczyzny i tym samym udaje się jej go "podciągnąć do góry" ("hinan zu ziehen", Goethe) oraz dać mu dostęp do "nieskończoności", "nieśmiertelności" i "wieczności". Czy jej teoretyczne pisma i jej działalność na rzecz emancypacji kobiet zaprzeczałyby jej tekstom literackim, na pierwszy rzut oka tak konwencjonalnym? W tym wykładzie podejmuję próbę odpowiedzi na to pytanie uważną lekturą jednego z jej najbardziej faustowskich opowiadań, mianowice "Czarna dziewanna".

God, the WTO – and hunger

Considering that endemic hunger is a consequence of poverty, and that food is arguably the most basic of all human needs, this book chapter shows one of the more prominent examples of rules and policy fragmentation but also one of the most blatant global governance problems. The three monotheistic religions Judaism, Christians and Islam are surprisingly unanimous about God’s prescriptions on hunger or, put theologically, on what can be said, or should be said, about the interpretations and traditions which, taken together, form the respective and differentiated traditions, identities and views of these beliefs on how to deal with poverty and hunger. A clear social ethos, in the form of global needs satisfaction, runs through both Jewish and Christian texts, and the Qur’an (Zakat). It confirms the value inversion between the world of the mighty and that of the hungry. The message is clear: because salvation is available only through the grace of God, those who have must give to those who have not. This is not charity: it is an inversion of values which can not be addressed by spending 0.7% of your GDP on ODA, and the implication of this sense of redistributive justice is that social offenders will be subject to the Last Judgement. Interestingly, these religious scriptures found their way directly into the human rights treaties adopted by the United Nations and ratified by the parliaments, as a legal base for the duty to protect, to respect and to remedy. On the other side the contradiction with international trade law is all the more flagrant, and it has a direct bearing on poverty: systematic surplus food dumping is still allowed under WTO rules, despite the declared objective ‘to establish a fair and market-oriented agricultural trading system’. A way forward would be a kind of ‘bottom up’ approach by focusing on extreme cases of food insecurity caused by food dumping, or by export restrictions where a direct effect of food insecurity in other countries can be established. Also, international financing institutions need to review their policies and lending priorities. The same goes for the bilateral investment treaties and a possible ‘public interest’ clause, at least in respect of agricultural land acquisitions in vulnerable countries. The bottom line is this: WTO rules cannot entail a right to violate other, equally binding treaty obligations when its membership as a whole claims to contribute to the Millennium Development Goals and pledges to eradicate extreme poverty and hunger.

Comparison of GOCE-GPS gravity fields derived by different approaches

Several techniques have been proposed to exploit GNSS-derived kinematic orbit information for the determination of long-wavelength gravity field features. These methods include the (i) celestial mechanics approach, (ii) short-arc approach, (iii) point-wise acceleration approach, (iv) averaged acceleration approach, and (v) energy balance approach. Although there is a general consensus that—except for energy balance—these methods theoretically provide equivalent results, real data gravity field solutions from kinematic orbit analysis have never been evaluated against each other within a consistent data processing environment. This contribution strives to close this gap. Target consistency criteria for our study are the input data sets, period of investigation, spherical harmonic resolution, a priori gravity field information, etc. We compare GOCE gravity field estimates based on the aforementioned approaches as computed at the Graz University of Technology, the University of Bern, the University of Stuttgart/Austrian Academy of Sciences, and by RHEA Systems for the European Space Agency. The involved research groups complied with most of the consistency criterions. Deviations only occur where technical unfeasibility exists. Performance measures include formal errors, differences with respect to a state-of-the-art GRACE gravity field, (cumulative) geoid height differences, and SLR residuals from precise orbit determination of geodetic satellites. We found that for the approaches (i) to (iv), the cumulative geoid height differences at spherical harmonic degree 100 differ by only ≈10 % ; in the absence of the polar data gap, SLR residuals agree by ≈96 % . From our investigations, we conclude that real data analysis results are in agreement with the theoretical considerations concerning the (relative) performance of the different approaches.

Improved star camera attitude data and their effect on the gravity field

Efforts are ongoing to decrease the noise of the GRACE gravity field models and hence to arrive closer to the GRACE baseline. The most significant error sources belong the untreated errors in the observation data and the imperfections in the background models. The recent study (Bandikova&Flury,2014) revealed that the current release of the star camera attitude data (SCA1B RL02) contain noise systematically higher than expected by about a factor 3-4. This is due to an incorrect implementation of the algorithms for quaternion combination in the JPL processing routines. Generating improved SCA data requires that valid data from both star camera heads are available which is not always the case because the Sun and Moon at times blind one camera. In the gravity field modeling, the attitude data are needed for the KBR antenna offset correction and to orient the non-gravitational linear accelerations sensed by the accelerometer. Hence any improvement in the SCA data is expected to be reflected in the gravity field models. In order to quantify the effect on the gravity field, we processed one month of observation data using two different approaches: the celestial mechanics approach (AIUB) and the variational equations approach (ITSG). We show that the noise in the KBR observations and the linear accelerations has effectively decreased. However, the effect on the gravity field on a global scale is hardly evident. We conclude that, at the current level of accuracy, the errors seen in the temporal gravity fields are dominated by errors coming from sources other than the attitude data.

Time variable Earth’s gravity field from SLR satellites

The time variable Earth’s gravity field contains information about the mass transport within the system Earth, i.e., the relationship between mass variations in the atmosphere, oceans, land hydrology, and ice sheets. For many years, satellite laser ranging (SLR) observations to geodetic satellites have provided valuable information of the low-degree coefficients of the Earth’s gravity field. Today, the Gravity Recovery and Climate Experiment (GRACE) mission is the major source of information for the time variable field of a high spatial resolution. We recover the low-degree coefficients of the time variable Earth’s gravity field using SLR observations up to nine geodetic satellites: LAGEOS-1, LAGEOS-2, Starlette, Stella, AJISAI, LARES, Larets, BLITS, and Beacon-C. We estimate monthly gravity field coefficients up to degree and order 10/10 for the time span 2003–2013 and we compare the results with the GRACE-derived gravity field coefficients. We show that not only degree-2 gravity field coefficients can be well determined from SLR, but also other coefficients up to degree 10 using the combination of short 1-day arcs for low orbiting satellites and 10-day arcs for LAGEOS-1/2. In this way, LAGEOS-1/2 allow recovering zonal terms, which are associated with long-term satellite orbit perturbations, whereas the tesseral and sectorial terms benefit most from low orbiting satellites, whose orbit modeling deficiencies are minimized due to short 1-day arcs. The amplitudes of the annual signal in the low-degree gravity field coefficients derived from SLR agree with GRACE K-band results at a level of 77 %. This implies that SLR has a great potential to fill the gap between the current GRACE and the future GRACE Follow-On mission for recovering of the seasonal variations and secular trends of the longest wavelengths in gravity field, which are associated with the large-scale mass transport in the system Earth.

Circulating FABP4 Is a Prognostic Biomarker in Patients With Acute Coronary Syndrome but Not in Asymptomatic Individuals.

OBJECTIVE Blood-borne biomarkers reflecting atherosclerotic plaque burden have great potential to improve clinical management of atherosclerotic coronary artery disease and acute coronary syndrome (ACS). APPROACH AND RESULTS Using data integration from gene expression profiling of coronary thrombi versus peripheral blood mononuclear cells and proteomic analysis of atherosclerotic plaque-derived secretomes versus healthy tissue secretomes, we identified fatty acid-binding protein 4 (FABP4) as a biomarker candidate for coronary artery disease. Its diagnostic and prognostic performance was validated in 3 different clinical settings: (1) in a cross-sectional cohort of patients with stable coronary artery disease, ACS, and healthy individuals (n=820), (2) in a nested case-control cohort of patients with ACS with 30-day follow-up (n=200), and (3) in a population-based nested case-control cohort of asymptomatic individuals with 5-year follow-up (n=414). Circulating FABP4 was marginally higher in patients with ST-segment-elevation myocardial infarction (24.9 ng/mL) compared with controls (23.4 ng/mL; P=0.01). However, elevated FABP4 was associated with adverse secondary cerebrovascular or cardiovascular events during 30-day follow-up after index ACS, independent of age, sex, renal function, and body mass index (odds ratio, 1.7; 95% confidence interval, 1.1-2.5; P=0.02). Circulating FABP4 predicted adverse events with similar prognostic performance as the GRACE in-hospital risk score or N-terminal pro-brain natriuretic peptide. Finally, no significant difference between baseline FABP4 was found in asymptomatic individuals with or without coronary events during 5-year follow-up. CONCLUSIONS Circulating FABP4 may prove useful as a prognostic biomarker in risk stratification of patients with ACS.