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Energetic particle precipitation leads to ionization in the Earth's atmosphere, initiating the formation of active chemical species which destroy ozone and have the potential to impact atmospheric composition and dynamics down to the troposphere. We report on one exceptionally strong high-energy electron precipitation event detected by balloon measurements in geomagnetic midlatitudes on 14 December 2009, with ionization rates locally comparable to strong solar proton events. This electron precipitation was possibly caused by wave–particle interactions in the slot region between the inner and outer radiation belts, connected with still poorly understood natural phenomena in the magnetosphere. Satellite observations of odd nitrogen and nitric acid are consistent with widespread electron precipitation into magnetic midlatitudes. Simulations with a 3D chemistry–climate model indicate the almost complete destruction of ozone in the upper mesosphere over the region where high-energy electron precipitation occurred. Such an extraordinary type of energetic particle precipitation can have major implications for the atmosphere, and their frequency and strength should be carefully studied.

For 2 decades, meteor radars have been routinely used to monitor atmospheric temperature around 90 km altitude. A common method, based on a temperature gradient model, is to use the height dependence of meteor decay time to obtain a height-averaged temperature in the peak meteor region. Traditionally this is done by fitting a linear regression model in the scattered plot of log⁡10(1/τ) and height, where τ is the half-amplitude decay time of the received signal. However, this method was found to be consistently biasing the slope estimate. The consequence of such a bias is that it produces a systematic offset in the estimated temperature, thus requiring calibration with other co-located measurements. The main reason for such a biasing effect is thought to be due to the failure of the classical regression model to take into account the measurement error in τ and the observed height. This is further complicated by the presence of various geophysical effects in the data, as well as observational limitation in the measuring instruments. To incorporate various error terms in the statistical model, an appropriate regression analysis for these data is the errors-in-variables model. An initial estimate of the slope parameter is obtained by assuming symmetric error variances in normalised height and log⁡10(1/τ). This solution is found to be a good prior estimate for the core of this bivariate distribution. Further improvement is achieved by defining density contours of this bivariate distribution and restricting the data selection process within higher contour levels. With this solution, meteor radar temperatures can be obtained independently without needing any external calibration procedure. When compared with co-located lidar measurements, the systematic offset in the estimated temperature is shown to have reduced to 5 % or better on average.

Polar mesospheric summer echoes (PMSEs) have been long associated with noctilucent clouds (NLCs). For large ice particles sizes and relatively high ice densities, PMSEs at 3 m Bragg wavelengths are known to be good tracers of the atmospheric wind dynamics and to be highly correlated with NLC occurrence. Combining the Middle Atmosphere ALOMAR Radar System (MAARSY) and the Kilpisjärvi Atmospheric Imaging Receiver Array (KAIRA), i.e., monostatic and bistatic observations, we show for the first time direct evidence of limited-volume PMSE structures drifting more than 90 km almost unchanged. These structures are shown to have horizontal widths of 5–15 km and are separated by 20–60 km, consistent with structures due to atmospheric waves previously observed in NLCs from the ground and from space. Given the lower sensitivity of KAIRA, the observed features are attributed to echoes from regions with high Schmidt numbers that provide a large radar cross section. The bistatic geometry allows us to determine an upper value for the angular sensitivity of PMSEs at meter scales. We find no evidence for strong aspect sensitivity for PMSEs, which is consistent with recent observations using radar imaging approaches. Our results indicate that multi-static all-sky interferometric radar observations of PMSEs could be a powerful tool for studying mesospheric wind fields within large geographic areas.

Sodankylä Geophysical Observatory has been operating a receiver network for ionospheric tomography and collecting the produced data since 2003. The collected data set consists of phase difference curves measured from COSMOS navigation satellites from the Russian Parus network (Wood and Perry, 1980) and tomographic electron density reconstructions obtained from these measurements. In this study vertical total electron content (VTEC) values are integrated from the reconstructed electron densities to make a qualitative and quantitative analysis to validate the long-term performance of the tomographic system. During the observation period, 2003–2014, there were three to five operational stations at the Fennoscandia sector. Altogether the analysis consists of around 66 000 overflights, but to ensure the quality of the reconstructions, the examination is limited to cases with descending (north to south) overflights and maximum elevation over 60°. These constraints limit the number of overflights to around 10 000. Based on this data set, one solar cycle of ionospheric VTEC estimates is constructed. The measurements are compared against the International Reference Ionosphere (IRI)-2012 model, F10.7 solar flux index and sunspot number data. Qualitatively the tomographic VTEC estimate corresponds to reference data very well, but the IRI-2012 model results are on average 40 % higher than that of the tomographic results.

This paper presents a comparison between standard ionospheric parameters manually and automatically scaled from ionograms recorded at the high-latitude Sodankylä Geophysical Observatory (SGO, ionosonde SO166, 64.1° geomagnetic latitude), located in the vicinity of the auroral oval. The study is based on 2610 ionograms recorded during the period June–December 2013. The automatic scaling was made by means of the Autoscala software. A few typical examples are shown to outline the method, and statistics are presented regarding the differences between manually and automatically scaled values of F2, F1, E and sporadic E (Es) layer parameters. We draw the conclusions that: 1. The F2 parameters scaled by Autoscala, foF2 and M(3000)F2, are reliable. 2. F1 is identified by Autoscala in significantly fewer cases (about 50 %) than in the manual routine, but if identified the values of foF1 are reliable. 3. Autoscala frequently (30 % of the cases) detects an E layer when the manual scaling process does not. When identified by both methods, the Autoscala E-layer parameters are close to those manually scaled, foE agreeing to within 0.4 MHz. 4. Es and parameters of Es identified by Autoscala are in many cases different from those of the manual scaling. Scaling of Es at auroral latitudes is often a difficult task.

Two case studies of upper mesospheric and lower thermospheric (UMLT) high-latitude effects of solar X-ray flares are presented. Sodankylä Ion-neutral Chemistry Model (SIC) electron density profiles agree with D-region EISCAT and riometer observations, provided that the profiles of the most variable ionisable component, nitric oxide, are adjusted to compensate for NOx production during preceding geomagnetically active periods. For the M6-class flare of 27 April 2006, following a quiet period, the agreement with cosmic noise absorption observed by the Sodankylä riometers was within reasonable limits without adjustment of the [NO] profile. For the major (X17-class) event of 28 October 2003, following high auroral activity and solar proton events, the NO concentration had to be increased up to on the order of 108 cm−3 at the D-region minimum. Thus [NO] can in principle be measured by combining SIC with observations, if the solar spectral irradiance and particle precipitation are adequately known. As the two case events were short and modelled for high latitudes, the resulting neutral chemical changes are insignificant. However, changes in the model ion chemistry occur, including enhancements of water cluster ions.

In the upper atmosphere, greenhouse gases produce a cooling effect, instead of a warming effect. Increases in greenhouse gas concentrations are expected to induce substantial changes in the mesosphere, thermosphere, and ionosphere, including a thermal contraction of these layers. In this article we construct for the first time a pattern of the observed long-term global change in the upper atmosphere, based on trend studies of various parameters. The picture we obtain is qualitative, and contains several gaps and a few discrepancies, but the overall pattern of observed long-term changes throughout the upper atmosphere is consistent with model predictions of the effect of greenhouse gas increases. Together with the large body of lower atmospheric trend research, our synthesis indicates that anthropogenic emissions of greenhouse gases are affecting the atmosphere at nearly all altitudes between ground and space.

Ionosonde data from sixteen stations are used to study the semiannual and annual variations in the height of the ionospheric F2-peak, hmF2. The semiannual variation, which peaks shortly after equinox, has an amplitude of about 8 km at an average level of solar activity (10.7 cm flux = 140 units), both at noon and midnight. The annual variation has an amplitude of about 11 km at northern midlatitudes, peaking in early summer; and is larger at southern stations, where it peaks in late summer. Both annual and semiannual amplitudes increase with increasing solar activity by day, but not at night. The semiannual variation in hmF2 is unrelated to the semiannual variation of the peak electron density NmF2, and is not reproduced by the CTIP and TIME-GCM computational models of the quiet-day thermosphere and ionosphere. The semiannual variation in hmF2 is approximately "isobaric", in that its amplitude corresponds quite well to the semiannual variation in the height of fixed pressure-levels in the thermosphere, as represented by the MSIS empirical model. The annual variation is not "isobaric". The annual mean of hmF2 increases with solar 10.7 cm flux, both by night and by day, on average by about 0.45 km/flux unit, rather smaller than the corresponding increase of height of constant pressure-levels in the MSIS model. The discrepancy may be due to solar-cycle variations of thermospheric winds. Although geomagnetic activity, which affects thermospheric density and temperature and therefore hmF2 also, is greatest at the equinoxes, this seems to account for less than half the semiannual variation of hmF2. The rest may be due to a semiannual variation of tidal and wave energy transmitted to the thermosphere from lower levels in the atmosphere.Key words: Atmospheric composition and structure (thermosphere - composition and chemistry) - Ionosphere (mid-latitude ionosphere)

This is a study of the negative ion chemistry in the mesosphere above Tromsø using a number of EISCAT observations of high energy proton precipitation events during the last solar maximum, and in particular around sunset on 23 October, 1989. In these conditions it is possible to look at the relative importance of the various photodetachment and photodissociation processes controlling the concentration of negative ions. The data analysed are from several UHF GEN11 determinations of the ion-plasma ACF together with the pseudo zero-lag estimate of the `raw' electron density, at heights between 55 km and 85 km, at less than 1 km resolution. The power profiles from the UHF are combined with the 55-ion Sodankylä model to obtain consistent estimates of the electron density, the negative ion concentrations, and the average ion mass with height. The neutral concentrations and ion temperature are given by the MSIS90 model. These parameters are then used to compare the calculated widths of the ion-line with the GEN11 determinations. The ion-line spectrum gives information on the effects of negative ions below 70 km where they are dominant; the spectral width is almost a direct measure of the relative abundance of negative ions.Key words. Ionosphere (auroral ionosphere; ion chemistry and composition; particle precipitation).

Severe burn patients lack adequate skin donor sites to resurface their burn wounds. Patients with severe burn injuries to areas such as an entire face are presently reconstructed with skin grafts that are inferior to normal facial skin. This study was designed in part to determine whether human skin allografts would survive, repopulate, and persist on patients with immunosuppression and after discontinuation of immunosuppression. Small split-thickness skin grafts were synchronously transplanted at the time of renal transplantation from six renal transplant donors to recipients. All six patients were immunosuppressed with the usual doses of renal transplant immunosuppressants (methylprednisolone, cyclosporine, prednisone, and azathioprine). The skin allografts were biopsied when rejection was suspected and at various intervals. Special histologic studies were performed on skin biopsy specimens. Class II DNA tissue typing was performed on transplanted and autogenous skin biopsy specimens of four patients. Fluorescent in situ hybridization was performed successfully on skin biopsies of four patients' transplanted skin and on two of these four patients' autogenous skin. All six human skin allografts sustained a 100 percent take and long-term clinical survival. DNA tissue typing performed on skin allograft biopsy specimens from patients taking immunosuppressants all revealed donor and recipient cells. DNA tissue typing performed on autogenous skin biopsies from the same patients all revealed only recipient cells. Fluorescent in situ hybridization performed on allograft and autogenous specimens from patients taking immunosuppressants revealed transplanted donor cells with rare recipient cells in the allograft and only recipient cells in the autogenous skin. This study of six patients proves that it is possible for human skin allografts to survive indefinitely on patients taking the usual dosages of immunosuppressants used for renal transplantation. There was minimal repopulation of skin allografts by autogenous keratinocytes and fibroblast while patients were taking immunosuppressants. Immunosuppression was discontinued in two patients after renal transplant rejection after 6 weeks and 5 years. When immunosuppression was discontinued after 5 years in one patient, the skin allograft cells were destroyed and replaced with autogenous cells, but the skin graft did not reject acutely and persisted clinically. It is hypothesized that the acellular portion of the skin allograft was not rejected acutely because of relatively low antigenicity and because it acted as a lattice for autogenous cells to migrate into and replace rejected allograft skin cells. No chimerism was seen in autogenous skin in the skin-renal transplant patients in this study.

Granulocyte colony-stimulating factor (G-CSF) has proven effective in the prophylaxis of chemotherapy-induced neutropenia and as a mobilizer of peripheral blood progenitor cells. The longevity of G-CSF action is limited by its removal from the body by two mechanisms. The first is thought to be mediated via receptors (receptor mediated clearance [RMC]) predominantly on neutrophils, the second process is likely the result of renal clearance. With the intention of developing a novel form of Filgrastim (r-met HuG-CSF) with a sustained duration of action in vivo, a new derivative named SD/01 has been made by association of Filgrastim with poly(ethylene glycol). The desired properties of this new agent would include a prolonged duration of action sufficient to cover a complete single course of chemotherapy. SD/01 is shown here to sustain significantly elevated neutrophil counts in hematopoietically normal mice for 5 days. In neutropenic mice effects were noted for at least 9 days, accompanying a significant reduction in the duration of chemotherapy induced neutropenia. Normal human volunteers showed higher than baseline ANC for around 9 to 10 days after a single injection of SD/01. Data from these normal volunteers also indicate that mobilization of CD34+ cells and progenitors may occur in a more timely manner and to around the same absolute numbers as with repeated daily injections of unmodified Filgrastim. These data indicate that SD/01 represents an efficacious novel form of Filgrastim with actions sustained for between one and two weeks from a single injection.

The intestinal carcinoid tumors of 26 patients were stained for the presence of serotonin, gastrin, somatostatin, motilin, secretin, glucagon, pancreatic polypeptide, ACTH, and neurotensin. Argentaffin and argyrophil stains were also performed in all cases. Thirty-five separate tumors (counting metastases and multiple primaries) from the 26 patients were studied. Serotonin was present in 30 of the 35 tumors. Nineteen tumors contained serotonin only. Fourteen tumors contained multiple neuroendocrine products. One tumor contained gastrin only. One tumor did not stain immunohistochemically, but was argyrophilic. Metastatic deposits were studied in nine patients. Some metastases produced the identical neuroendocrine products as the primary tumor, whereas others produced either additional or fewer hormones than the primary tumor. Moreover, different metastases from the same primary tumor were observed to produce different hormones. Argyrophilic cells were present in all cases and were much more numerous than cells staining by immunohistochemistry. Argyrophilic cells probably contain monoamines and polypeptide hormones in addition to those studied in this series. The argyrophil stain was the best general stain in this study for the demonstration of neuroendocrine cells. Argentaffin staining was negative in ten cases that were serotonin positive and two argentaffin positive cases were serotonin negative. The carcinoid syndrome, as clinically defined by the presence of flushing and diarrhea, was noted in five patients, all of whom had serotonin-containing small bowel carcinoids. Endocrine-related symptoms were not clinically appreciated in the remaining patients.

A peculiar branched cylindrical structure within the nuclei of human osteosarcoma cells is reported. Although the described structures may be postulated to represent either "vermicellar bodies" or a response to cellular injury by chemotherapeutic agents, their origin and function are unknown to us.

Primary gastrin cell hyperfunction of the gastric antrum as a clinical syndrome consists of basal hypergastrinemia, an exaggerated gastrin response to feeding, the absence of any ectopic source of gastrin secretion, and peptic ulcer disease. The number of G-cells were quantitated in the gastric antrum of five patients with clinically diagnosed primary G-cell hyperfunction, and the results were compared to controls with a variety of gastric diseases. Patients with the clinical diagnosis of primary G-cell hyperfunction had a significantly increased number of antral G-cells (p less than 0.05). The clinical syndrome of primary G-cell hyperplasia appears to be associated with hyperplasia of G-cells rather than with the hypersecretion of gastrin by a normal number of G-cells.

Purified splenic macrophage (M phi) from normal DBA/2J mice and mice bearing P815 tumors were examined for responsiveness to lymphokine (LK) preparations containing high concentrations of IFN-gamma. For both normal and tumor-bearing M phi, LK treatment induced morphologic changes and increased the percentage of Ia+ cells from 35 to 55%. Although neither population exhibited spontaneous cytotoxicity toward P815 targets, LK treatment induced considerable tumoricidal activity in tumor-bearing M phi (32 to 80% lysis) but only minimal activity in normal M phi (8 to 17% lysis). Subcutaneous injection of 1 X 10(6)P815 cells into DBA/2J led to progressive tumor growth and death of 100% of the recipients after 27 +/- 3 days. Injection of a 1:18 mixture of P815 with either LK-activated normal or tumor-bearing M phi caused tumor regression after 10 days, and prolonged life until 43 +/- 4 days with tumor-bearing M phi and 39 +/- 3 days with normal M phi. Untreated normal or tumor-bearing M phi were unable to cause the effect (30 +/- 2 days), and lymphocytes could not be substituted for M phi (25 +/- 3 days). In x-irradiated recipients, no effect of LK-activated M phi could be observed (control = 19 +/- 2 days; LK-activated tumor-bearing M phi = 21 +/- 3 days). In addition, administration of an admixture of LK-treated M phi and x-rayed tumor before challenge with viable P815 enabled the recipient to inhibit tumor growth and caused tumor necrosis with inflammatory cell infiltration of the tumor. These observations suggest that, in part, LK-activated M phi may interact in vivo with host-derived cellular components and enhance the immune reactivity of the host against the tumor.

Several large pulmonary lesions were found in a 45-year-old woman after therapy for a typical tibial giant cell tumor. The pulmonary lesions were incidentally found during a routine chest examination four years after the original bone tumor had been found. Removal of the lung lesions showed ordinary giant cell tumor identical to the primary bone tumor, with no evidence of sarcomatous transformation. After an analysis of 12 other well-documented cases in the world literature, we postulate that the lung lesions in this case probably represent benign "metastases;" i.e., benign tumor implants compatable with a good long-term prognosis, rather than the usual lethal course associated with the vast majority of metastatic malignancies.

Isolation of polymorphonuclear leukocytes (PMN) provides an opportunity to study PMN activity in vitro and to label PMN for study of in vivo kinetics. However, simple phlebotomy (SP) of a small animal frequently yields too few PMN for in vitro handling, while PMN harvested from an induced-peritonitis may not accurately reflect PMN in a less stimulated state. We report a novel method of harvesting PMN from the circulation of rats, using hetastarch exchange transfusion (HET), which is both time and animal sparing. HET harvested 8-fold more PMN than SP. In vitro cell function was examined with assays of adherence, chemotaxis, bacterial killing, and superoxide generation. No significant (p less than 0.05) difference was found between PMN obtained by HET and pooled-PMN obtained by SP. In vivo function was examined following labeling with indium111-oxine. The kinetics pattern described suggested normal migratory activity when compared to previous reports. The data demonstrate that rats possess a relatively large, noncirculating pool of PMN which is readily accessible by HET.

A case of pancreatic tumor with features of both an acinar cell and an endocrine cell tumor is presented. The histologic appearance of the tumor by light microscopy was consistent with the appearance of either an islet cell tumor or an acinar cell tumor. Electron microscopy revealed two distinct populations of membrane bound granules within the same tumor cells; namely, a small granule measuring 100-200 nanometers in diameter with a narrow halo separating it from the granule membrane, and a large granule measuring 400-500 nanometers in diameter and having a closely applied membrane. The smaller granules have the characteristic appearance of gastroenteropancreatic (GEP) endocrine-cell granules. The large granules are greater in size than neuroendocrine granules, their morphologic structure is most consistent with that of zymogen granules, and a positive lipase stain supported the presence of zymogen granules within the tumor. The occurrence of both neuroendocrine and zymogen granules within the same cell has been previously described in the "intermediate cell" of the pancreas, but not to our knowledge in a tumor of the pancreas. The finding of both endocrine and exocrine granules within a single cell indicates a histogenetic relationship between the pancreatic endocrine and exocrine cells, and may represent the first reported case of a neoplastic proliferation of intermediate cells.

Antisera raised against serotonin, gastrin, somatostastin, motilin, bombesin, calcitonin, secretin, glucagon, ACTH, neurotensin, and pancreatic polypeptide carboxyterminal hexapeptide were employed to immunohistochemically stain seven pulmonary carcinoids. Argentaffin and argyrophil stains were also performed on all cases. Serotonin-like immunoreactivity was present in four tumors, pancreatic polypeptide-like immunoreactivity in four tumors, bombesin-like immunoreactivity in two tumors and ACTH-like immunoreactivity in one tumor. The cells shown to contain neuroendocrine products constituted a minority cell population in all tumors except the ACTH-immunoreactive tumor. This study suggests that pulmonary carcinoids, like their abdominal counterparts, contain a variety of neuroendocrine products, and may produce more than one neuroendocrine product. Serotonin and pancreatic polypeptide-like immunoreactivity were the most prevalent neuroendocrine products demonstrable in this study.

Fifteen neuroendocrine carcinomas of the skin (Merkel cell tumors) were stained within the constraints of tissue availability by the Grimelius method and immunohistochemically for keratin, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), S-100, common leukocyte antigen (CLA), met-enkephalin, bombesin, calcitonin, ACTH, gastrin, and somatostatin. Focal argyrophilia was present in 5 of 12 tumors. All tumors tested demonstrated immunoreactivity for NSE and 5 tumors were positive for keratin. One tumors appeared to demonstrate focal ACTH-like immunoreactivity, but otherwise no immunoreactivity for the above mentioned polypeptide hormones was noted in 11 completely studied tumors. One tumor contained histologically obvious areas of squamous differentiation in addition to areas of Merkel cell tumor. In various tumors, keratin immunoreactivity was present either in areas of histologically obvious squamous differentiation, in randomly scattered single cells not histologically identifiable as squamous, or in a paranuclear dot-like distribution. Immunoreactivity for CEA, S-100 and CLA was not present in any tumors. The lack of met-enkephalin and the presence of squamous differentiation in these tumors indicates multidirectional differentiation in a fashion not phenotypically typical of Merkel cells.