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Myeloproliferative neoplasms (MPNs), a group of malignant hematological disorders, occur as a consequence of somatic mutations in the hematopoietic stem cell compartment and show excessive accumulation of mature myeloid cells in the blood. A major cause of morbidity and mortality in these patients is the marked prothrombotic state leading to venous and arterial thrombosis, including myocardial infarction (MI), deep vein thrombosis (DVT), and strokes. Additionally, many MPN patients suffer from inflammation-mediated constitutional symptoms, such as fever, night sweats, fatigue, and cachexia. The chronic inflammatory syndrome in MPNs is associated with the up-regulation of various inflammatory cytokines in patients and is involved in the formation of the so-called MPN thromboinflammation. JAK2-V617F, the most prevalent mutation in MPNs, has been shown to activate a number of integrins on mature myeloid cells, including granulocytes and erythrocytes, which increase adhesion and drive venous thrombosis in murine knock-in/out models. This review aims to shed light on the current understanding of thromboinflammation, involvement of neutrophils in the prothrombotic state, plausible molecular mechanisms triggering the process of thrombosis, and potential novel therapeutic targets for developing effective strategies to reduce the MPN disease burden.

Summary The aim of the present study was to investigate the pathology of feline myocardial fibrosis. The hearts from 40 cats with myocardial fibrosis were compared with the hearts from 25 normal cats. Clinical data were available in 11 cases. Hearts with myocardial fibrosis were hypomotile and there were hyperechoic areas in the ventricular wall on echocardiography. The presence of myocardial fibrosis was correlated significantly with hypertrophy of the ventricles, atrial dilation and angiosclerosis. Immunohistochemical studies demonstrated that normal feline cardiomyocytes expressed matrix metalloproteinase (MMP)-2, MMP-9, MMP-14, tissue inhibitor of matrix metalloproteinase (TIMP)-2 and transforming growth factor (TGF)-β2. Fibroblasts in normal hearts expressed only TIMP-2. In the hearts with myocardial fibrosis, expression of MMP-2, TIMP-3 and TGF-β2 by cardiomyocytes was significantly increased, but TIMP-2 expression was diminished. Fibroblasts in the affected hearts showed expression of MMP-14 in several cases. These findings suggest that a complex fibrotic remodelling of the feline myocardium occurs in this disease and that cardiomyocytes are involved in this process.

Numerous studies have shown that the opiate system is crucially involved in emotionally guided behavior. In the present study, we focussed on the medio-rostral neostriatum/hyperstriatum ventrale (MNH) of the chick forebrain. This avian prefrontal cortex analogue is critically involved in auditory filial imprinting, a well-characterized juvenile emotional learning event. The high density of mu-opiate receptors expressed in the MNH led to the hypothesis that mu-opiate receptor-mediated processes may modulate the glutamatergic, dopaminergic, and/or serotonergic neurotransmission within the MNH and thereby have a critical impact on filial imprinting. Using microdialysis and pharmaco-behavioral approaches in young chicks, we demonstrated that: the systemic application of the mu-opiate receptor antagonist naloxone (5, 50 mg/kg) significantly increased extracellular levels of 5-HIAA and HVA; the systemic application of the specific mu-opiate receptor agonist DAGO (5 mg/kg) increased the levels of HVA and taurine, an effect that was antagonized by simultaneously applied naloxone (5 mg/kg); the local application of DAGO (1 mM) had no effects on 5-HIAA, HVA, glutamate, and taurine, however, the effects of systemically injected naloxone (5 mg/kg) were abolished by simultaneously applied DAGO (1 mM); the systemic application of naloxone (5 mg/kg) increased distress behavior (measured as the duration of distress vocalization during separation from the peer group). These results are in line with our hypothesis that the mu-opiate receptor-mediated modulation of serotonergic and dopaminergic neurotransmission alters the emotional and motivational status of the animal and thereby may play a modulatory role during filial imprinting in the newborn animal.

Alzheimer's disease is a neurodegenerative disorder characterized by a loss of memory and spatial orientation. It is also reported that the dopamine system is affected. Dopamine plays a prominent role in motor functions, motivation, emotion, arousal and reward, and it is important for learning and memory. One model that represents characteristic hallmarks of Alzheimer's disease is the 5xFAD mouse model, in which parenchymal plaque load starts at 2months of age. Transgenic 5xFAD mice show the first behavioral deficits at 6months, which are evident at 9months of age. In this study, we investigated the pharmacological influence of methylphenidate (MPH) on behavioral deficits of 5xFAD mice. Using a battery of behavioral tests, we observed no influence of MPH on anxiety in the elevated plus maze, whereas the locomotion and explorative activity in the open field was increased in transgenic and non-transgenic 5xFAD mice after the application of MPH. Further MPH inhibits habituation in the open field in healthy 5xFAD littermates after the application of 10mg/kg MPH. On the other hand, 10mg/kg MPH improved spatial memory in 6-month-old transgenic 5xFAD males, i.e., at a time point when deficits start to occur. However, in 9-month-old transgenic mice, MPH did not improve persisting learning and memory deficits. We concluded that MPH might improve the non-cognitive, apathy-like behavior (indicated by a reduced exploration), but it has no influence on sustained Alzheimer typical learning and memory deficits.

Transgenic animal models of Alzheimer's disease (AD) are widely used to investigate mechanisms of pathophysiology and cognitive dysfunctions. A model with a very early development of parenchymal plaque load at the age of 2months is the 5xFAD mouse (Tg6799, Oakley et al. 2006). These 5xFAD mice over-express both human amyloid precursor protein (APP) and human presenilin 1 (PS1). Mice from this line have a high APP expression correlating with a high burden and an accelerated accumulation of the 42 amino acid species of amyloid-β (Aβ). The aim of this study was the behavioral and functional investigations of 5xFAD males because in most studies females of this strain were characterized. In comparison to literature of transgenic 5xFAD females, transgenic 5xFAD males showed decreased anxiety in the elevated plus maze, reduced locomotion and exploration in the open field and disturbances in learning performance in the Morris water maze starting at 9months of age. Electroencephalogram (EEG) recordings on 6month old transgenic mice revealed a decrease of delta, theta, alpha, beta and gamma frequency bands whereas the subdelta frequency was increased. EEG recordings during sleep showed a reduction of rapid eye movement sleep in relation to the amount of total sleep. Thus, 5xFAD males develop early functional disturbances and subsequently behavioral deficits and therefore they are a good mouse model for studying Alzheimer's disease.

Northrop Grumman Aerospace Systems (NGAS) has a long legacy developing and fielding hyperspectral sensors, including airborne and space based systems covering the visible through Long Wave Infrared (LWIR) wavelength ranges. Most recently NGAS has developed the Hyperspectral Airborne Terrestrial Instrument (HATI) family of hyperspectral sensors, which are compact airborne hyperspectral imagers designed to fly on a variety of platforms and be integrated with other sensors in NGAS's instrument suite. The current sensor under development is the HATI-2500, a full range Visible Near Infrared (VNIR) through Short Wave Infrared (SWIR) instrument covering the 0.4 - 2.5 micron wavelength range with high spectral resolution (3nm). The system includes a framing camera integrated with a GPS/INS to provide high-resolution multispectral imagery and precision geolocation. Its compact size and flexible acquisition parameters allow HATI-2500 to be integrated on a large variety of aerial platforms. This paper describes the HATI-2500 sensor and subsystems and its expected performance specifications.

We demonstrate a numerical technique for registering multiple frames of point cloud data from an airborne 3D flash ladar system that we have designed, built, and flown. This technique stitches together ladar data even in the presence of inaccuracies in the line-of-sight pointing knowledge as well as instabilities in the time-of-flight clock frequency. The technique performs frame-to-frame in-track as well as cross-track stitching of multiple flight line data to create large area maps of urban areas and vegetation. Filters remove data with spurious range values and high intensity specular back flashes such as those from bodies of water. Signal averaging of nearly overlapping pixel data creates monolithic, wide area 3D maps that are geo-located and thus readily superimposable with other types of sensor data, such as hyperspectral images, for fused-data exploitations. The accuracy of the numerical technique used for stitching data from different target types, such as urban, vegetation, or bare earth, was studied. This analysis provides guidance for future improvements of algorithms used for registering airborne 3D flash ladar point cloud data sets.

Northrop Grumman Aerospace Systems (NGAS) has developed the Hyperspectral Airborne Tactical Instrument (HATI), a compact airborne hyperspectral imager designed to fly on a variety of platforms and to be integrated with other sensors in the NGAS instrument suite. HATI has taken part in a variety of missions and flown in conjunction with other NGAS airborne sensors including the recently-developed NGAS 3-D flash ladar system to demonstrate a multi-sensor data fusion approach. HATI is a push-broom sensor which gathers information in the 400 nm to 1700 nm wavelength range. Its compact size allows HATI to be mounted on commercial-of-the-shelf (COTS) aerial photography stabilization platforms and on a large variety of aerial platforms. In its most recent flight season, the HATI sensor was used to gather data for applications including remote classification of vegetation, forests, and man-made materials. The HATI instrument has undergone laboratory and in-situ performance validation and radiometric calibration. This paper describes the HATI sensor and recent data collection campaigns.

Northrop Grumman Corporation (NGC) provides systems and technologies to ensure national security based on technologies - from undersea to outer space, and in cyberspace. With a heritage of developing and integrating science instruments on space platforms and airborne systems, NGC is conducting analysis of alternatives for a global observing system that integrates data collected from geostationary and polar-orbiting satellites with Unmanned Aerial System (UAS) platforms. This enhanced acquisition of environmental data will feed decision support systems such as the TouchTable ® to deliver improved decision making capabilities. Rapidly fusing and displaying multiple types of weather and ocean observations, imagery, and environmental data with geospatial data to create an integrated source of information for end users such as emergency managers and planners will deliver innovative solutions to improve disaster warning, mitigate disaster impacts, and reduce the loss of life and property. We present analysis of alternatives of combinations of sensor platforms that integrate space and airborne systems with ground and ocean observing sensors and form the basis for vertically integrated global observing systems with the capacity to improve measurements associated with hazard and climate-related uncertainties. The analyses include candidate sensors deployed on various configurations of satellites that include NPOESS, GOES R, and future configurations, augmented by UAS vehicles including Global Hawk, configured to deliver innovative environmental data collection capabilities over a range of environmental conditions, including severe hazards, such as hurricanes and extreme wildland fires. Resulting approaches are evaluated based on metrics that include their technical feasibility, capacity to be integrated with evolving Earth science models and relevant decision support tools, and life cycle costs.

Die Gehalte an F, Al, Cl, Cr, Fe, Co, Cu, Zn, Se, Ag, I und Au sind im Haar aktivicrungsanalytisch bestimmt und mit Werten aus der Literatur verglichen worden. Dabei fanden wir einen relativ niedrigen Se-Gehalt (0,3 ppm). Wir erhielten, erhohte Konzentrationen an Cr und Mn im Haar von Schweisern und hohe Werte fur F bei Personen, die mit Fluorverbindungen arbeiten. Frauen mit einem Mamma- bzw. Schilddrusenkarzinom zeigten erhohte Zn-Werte und Struma-patienten erniedrigte I-Gehalte im Haar.

NAA investigations of the trace-elements zinc and copper have been performed purposing to settle the problems of distinction between healthy persons and patients suffering from malignant ailments on the one hand and between malignant diseases of different origin on the other hand. Mean values and scattering ranges have been ascertained as well as the zinc-copper-quotient and significance checks of the standard group. For all the malignant neoplasms mentioned before the zinc-values show a significant increase (γ=5%). Significant increases of the copper-values could only be proven in cases of carcinomas of the mamma and of the thyroid gland. A significant increase of the zinc-copper-quotient could be noticed in cases of cancer of the rectum and the malignant melanomas. The possibly early diagnosis by means of trace-element-determination has been shown in three cases.

For the prognosis of the relatively rare bone tumours the time of neglect has an essential importance. At every suspicion of a bone tumour a systematic diagnostics which is directed to the clarification of the malignity should be carried out. The anamnesis often contains references which particularly allow an early recognition of the disease. Only the synopsis of anamnestic, clinical and paraclinical, radiological and bioptical findings ascertains the correct diagnosis. The modern diagnostic methods are discussed concerning their differential-diagnostic valency and range of indications. The close collaboration between peripheral and central institutions on the one hand and between surgeons, radiologists and pathologists on the other is necessary to make a certain diagnosis of the bone tumour in shortest time. A national and central register of cases of bone tumours would be recommendable.