Macro Monte Carlo for dose calculation of proton beams

Although the Monte Carlo (MC) method allows accurate dose calculation for proton radiotherapy, its usage is limited due to long computing time. In order to gain efficiency, a new macro MC (MMC) technique for proton dose calculations has been developed. The basic principle of the MMC transport is a local to global MC approach. The local simulations using GEANT4 consist of mono-energetic proton pencil beams impinging perpendicularly on slabs of different thicknesses and different materials (water, air, lung, adipose, muscle, spongiosa, cortical bone). During the local simulation multiple scattering, ionization as well as elastic and inelastic interactions have been taken into account and the physical characteristics such as lateral displacement, direction distributions and energy loss have been scored for primary and secondary particles. The scored data from appropriate slabs is then used for the stepwise transport of the protons in the MMC simulation while calculating the energy loss along the path between entrance and exit position. Additionally, based on local simulations the radiation transport of neutrons and the generated ions are included into the MMC simulations for the dose calculations. In order to validate the MMC transport, calculated dose distributions using the MMC transport and GEANT4 have been compared for different mono-energetic proton pencil beams impinging on different phantoms including homogeneous and inhomogeneous situations as well as on a patient CT scan. The agreement of calculated integral depth dose curves is better than 1% or 1 mm for all pencil beams and phantoms considered. For the dose profiles the agreement is within 1% or 1 mm in all phantoms for all energies and depths. The comparison of the dose distribution calculated using either GEANT4 or MMC in the patient also shows an agreement of within 1% or 1 mm. The efficiency of MMC is up to 200 times higher than for GEANT4. The very good level of agreement in the dose comparisons demonstrate that the newly developed MMC transport results in very accurate and efficient dose calculations for proton beams.

Consequences of depleted SERCA2-gated calcium stores in the skin

Sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) pumps belong to the family of Ca2+-ATPases responsible for the maintenance of calcium in the endoplasmic reticulum. In epidermal keratinocytes, SERCA2-controlled calcium stores are involved in cell cycle exit and onset of terminal differentiation. Hence, their dysfunction was thought to provoke impaired keratinocyte cohesion and hampered terminal differentiation. Here, we assessed cultured keratinocytes and skin biopsies from a canine family with an inherited skin blistering disorder. Cells from lesional and phenotypically normal areas of one of these dogs revealed affected calcium homeostasis due to depleted SERCA2-gated stores. In phenotypically normal patient cells, this defect compromised upregulation of p21(WAF1) and delayed the exit from the cell cycle. Despite this abnormality it failed to impede the terminal differentiation process in the long term but instead coincided with enhanced apoptosis and appearance of chronic wounds, suggestive of secondary mutations. Collectively, these findings provide the first survey on phenotypic consequences of depleted SERCA-gated stores for epidermal homeostasis that explain how depleted SERCA2 calcium stores provoke focal lesions rather than generalized dermatoses, a phenotype highly reminiscent of the human genodermatosis Darier disease.

Biologically relevant sex differences for fitness-related parameters in active octogenarians

The number of elderly people is growing in western populations, but only few maximal performance data exist for people >75 years, in particular for European octogenarians. This study was performed to characterize maximal performance of 55 independently living subjects (32 women, 81.1 +/- 3.4 years; 23 men, 81.7 +/- 2.9 years) with a focus on sex differences. Maximal performance was determined in a ramp test to exhaustion on a bicycle ergometer with ergospirometry, electrocardiogram and blood lactate measurements. Maximal isometric extension strength of the legs (MEL) was measured on a force platform in a seated position. Body composition was quantified by X-ray absorptiometry. In >25% of the subjects, serious cardiac abnormalities were detected during the ramp test with men more frequently being affected than women. Maximal oxygen consumption and power output were 18.2 +/- 3.2 versus 25.9 +/- 5.9 ml min(-1) kg(-1) and 66 +/- 12 versus 138 +/- 40 W for women versus men, with a significant sex difference for both parameters. Men outperformed women for MEL with 19.0 +/- 3.8 versus 13.6 +/- 3.3 N kg(-1). Concomitantly, we found a higher proportion of whole body fat in women (32.1 +/- 6.2%) compared to men (20.5 +/- 4.4%). Our study extends previously available maximal performance data for endurance and strength to independently living European octogenarians. As all sex-related differences were still apparent after normalization to lean body mass, it is concluded that it is essential to differentiate between female and male subjects when considering maximal performance parameters in the oldest segment of our population.

Statistical evaluation of alternative models of human evolution

An appropriate model of recent human evolution is not only important to understand our own history, but it is necessary to disentangle the effects of demography and selection on genome diversity. Although most genetic data support the view that our species originated recently in Africa, it is still unclear if it completely replaced former members of the Homo genus, or if some interbreeding occurred during its range expansion. Several scenarios of modern human evolution have been proposed on the basis of molecular and paleontological data, but their likelihood has never been statistically assessed. Using DNA data from 50 nuclear loci sequenced in African, Asian and Native American samples, we show here by extensive simulations that a simple African replacement model with exponential growth has a higher probability (78%) as compared with alternative multiregional evolution or assimilation scenarios. A Bayesian analysis of the data under this best supported model points to an origin of our species approximately 141 thousand years ago (Kya), an exit out-of-Africa approximately 51 Kya, and a recent colonization of the Americas approximately 10.5 Kya. We also find that the African replacement model explains not only the shallow ancestry of mtDNA or Y-chromosomes but also the occurrence of deep lineages at some autosomal loci, which has been formerly interpreted as a sign of interbreeding with Homo erectus.

Percutaneous vein occlusion with small intestinal submucosa: an experimental pilot study in Swine and sheep

PURPOSE: The objective of this study was to investigate the feasibility, outcomes, and amount of small intestinal submucosa (SIS) material needed for embolization of jugular vein (JV) in a swine and sheep model. Our hypothesis was that SIS would cause vein occlusion. MATERIALS AND METHODS: The external JVs (EJV) in swine (n = 6) and JVs in sheep (n = 6) were occluded with SIS fan-folded compressed strips. After percutaneous puncture of the peripheral portion of the EJV or JV, a TIPS set was used to exit their lumen centrally through the skin. The SIS strips were delivered into the isolated venous segment with a pull-through technique via a 10-Fr sheath. Follow-up venograms were done immediately after placement and at the time of sacrifice at 1 or 3 months. Gross examinations focused on the EJV or JV and their surrounding structures. Specimens were evaluated by histology. RESULTS: SIS strip(s) placement was successful in all cases, with immediate vein occlusion seen in 23 of 24 veins (95.8%). All EJVs treated with two strips and all JVs treated with three or four strips remained closed on 1- and 3-month follow-up venograms. Two EJVs treated with one strip and one JV treated with two strips were partially patent on venograms at 1 and 3 months. There has been one skin inflammatory reaction. Necropsies revealed excluded EJV or JV segments with SIS incorporation into the vein wall. Histology demonstrated various stages of SIS remodeling with fibrocytes, fibroblasts, endothelial cells, capillaries, and inflammatory cells. CONCLUSION: We conclude that EJV and JV ablation with SIS strips using percutaneous exit catheterization is feasible and effective in animal models. Further exploration of SIS as vein ablation material is recommended.

Gunshot injuries detected by post-mortem multislice computed tomography (MSCT): a feasibility study

Modern cross-sectional imaging techniques are being increasingly implemented in forensic pathology. These methods may serve as an adjuvant to classic forensic autopsies or even replace them altogether in the future. In order to assess the practicability of such a method, namely post-mortem multislice computed tomography (MSCT) in fatal gunshot injuries, 22 corpses underwent such an examination prior to forensic autopsy. The cardinal questions of the location of entrance and exit wounds, the detection of bullets and bullet fragments in the body, the bullet course, inflicted injuries and cause of death were addressed at MSCT and autopsy. The results of the two techniques revealed that post-mortem MSCT can answer these questions reliably and is therefore a useful tool in the assessment of such injuries.

Diastolic dysfunction of the cardiac allograft and maximal exercise capacity

BACKGROUND: Peak oxygen uptake (peak Vo(2)) is an established integrative measurement of maximal exercise capacity in cardiovascular disease. After heart transplantation (HTx) peak Vo(2) remains reduced despite normal systolic left ventricular function, which highlights the relevance of diastolic function. In this study we aim to characterize the predictive significance of cardiac allograft diastolic function for peak Vo(2). METHODS: Peak Vo(2) was measured using a ramp protocol on a bicycle ergometer. Left ventricular (LV) diastolic function was assessed with tissue Doppler imaging sizing the velocity of the early (Ea) and late (Aa) apical movement of the mitral annulus, and conventional Doppler measuring early (E) and late (A) diastolic transmitral flow propagation. Correlation coefficients were calculated and linear regression models fitted. RESULTS: The post-transplant time interval of the 39 HTxs ranged from 0.4 to 20.1 years. The mean age of the recipients was 55 +/- 14 years and body mass index (BMI) was 25.4 +/- 3.9 kg/m(2). Mean LV ejection fraction was 62 +/- 4%, mean LV mass index 108 +/- 22 g/m(2) and mean peak Vo(2) 20.1 +/- 6.3 ml/kg/min. Peak Vo(2) was reduced in patients with more severe diastolic dysfunction (pseudonormal or restrictive transmitral inflow pattern), or when E/Ea was > or =10. Peak Vo(2) correlated with recipient age (r = -0.643, p < 0.001), peak heart rate (r = 0.616, p < 0.001) and BMI (r = -0.417, p = 0.008). Of all echocardiographic measurements, Ea (r = 0.561, p < 0.001) and Ea/Aa (r = 0.495, p = 0.002) correlated best. Multivariate analysis identified age, heart rate, BMI and Ea/Aa as independent predictors of peak Vo(2). CONCLUSIONS: Diastolic dysfunction is relevant for the limitation of maximal exercise capacity after HTx.

Seasonal variation of VO 2 max and the VO2-work rate relationship in elite Alpine skiers

PURPOSE: Alpine ski performance relates closely to both anaerobic and aerobic capacities. During their competitive season, skiers greatly reduce endurance and weight training, and on-snow training becomes predominant. To typify this shift, we compared exhaustive ramp cycling and squat (SJ) and countermovement jumping (CMJ) performance in elite males before and after their competitive season. RESULTS: In postseason compared with preseason: 1) maximal oxygen uptake (VO 2 max) normalized to bodyweight was higher (55.2 +/- 5.2 vs 52.7 +/- 3.6 mL x kg(-1) x min(-1), P < 0.01), but corresponding work rate (W) was unchanged; 2) at ventilatory thresholds (VT), absolute and relative work rates were similar but heart rates were lower; 3) VO2/W slope was greater (9.59 +/- 0.6 vs 9.19 +/- 0.4 mL O2 x min(-1) x W(-1), P = 0.02), with similar flattening (P < 0.01) above V T1 at both time points; and 4) jump height was greater in SJ (47.4 +/- 4.4 vs 44.7 +/- 4.3 cm, P < 0.01) and CMJ (52.7 +/- 4.6 vs 50.4 +/- 5.0 cm, P < 0.01). DISCUSSION: We believe that aerobic capacity and leg power were constrained in preseason and that improvements primarily reflected an in-season recovery from a fatigued state, which was caused by incongruous preseason training. Residual adaptations to high-altitude exposure in preseason could have also affected the results. Nonetheless, modern alpine skiing seemingly provides an ample cardiovascular training stimulus for skiers to maintain their aerobic capacities during the racing season. CONCLUSIONS: We conclude that aerobic fitness and leg explosiveness can be maintained in-season but may be compromised by heavy or excessive preseason training. In addition, ramp test V O2/W slope analysis could be useful for monitoring both positive and negative responses to training.

Modifying peripheral IV catheters with side holes and side slits results in favorable changes in fluid dynamic properties during the injection of iodinated contrast material

OBJECTIVE: The purpose of this study was to compare a standard peripheral end-hole angiocatheter with those modified with side holes or side slits using experimental optical techniques to qualitatively compare the contrast material exit jets and using numeric techniques to provide flow visualization and quantitative comparisons. MATERIALS AND METHODS: A Schlieren imaging system was used to visualize the angiocatheter exit jet fluid dynamics at two different flow rates. Catheters were modified by drilling through-and-through side holes or by cutting slits into the catheters. A commercial computational fluid dynamics package was used to calculate numeric results for various vessel diameters and catheter orientations. RESULTS: Experimental images showed that modifying standard peripheral IV angiocatheters with side holes or side slits qualitatively changed the overall flow field and caused the exiting jet to become less well defined. Numeric calculations showed that the addition of side holes or slits resulted in a 9-30% reduction of the velocity of contrast material exiting the end hole of the angiocatheter. With the catheter tip directed obliquely to the wall, the maximum wall shear stress was always highest for the unmodified catheter and was always lowest for the four-side-slit catheter. CONCLUSION: Modified angiocatheters may have the potential to reduce extravasation events in patients by reducing vessel wall shear stress.

Physiological response to increasing levels of neurally adjusted ventilatory assist (NAVA)

This study evaluated the response to increasing levels of neurally adjusted ventilatory assist (NAVA), a mode converting electrical activity of the diaphragm (EAdi) into pressure, regulated by a proportionality constant called the NAVA level. Fourteen rabbits were studied during baseline, resistive loading and ramp increases of the NAVA level. EAdi, airway (Paw) and esophageal pressure (Pes), Pes pressure time product (PTPes), breathing pattern, and blood gases were measured. Resistive loading increased PTPes and EAdi. P(a)(CO)(2) increased with high load but not during low load. Increasing NAVA levels increased Paw until a breakpoint where the Paw increase was reduced despite increasing NAVA level. At this breakpoint, Pes, PTPes, EAdi, and P(a)(CO)(2) were similar to baseline. Further increase of the NAVA level reduced Pes, PTPes and EAdi without changes in ventilation. In conclusion, observing the trend in Paw during a ramp increase of the NAVA level allows determination of a level where the inspiratory effort matches unloaded conditions.

Compound heterozygous mutations affect protein folding and function in patients with congenital sucrase-isomaltase deficiency

BACKGROUND & AIMS: Congenital sucrase-isomaltase (SI) deficiency is an autosomal-recessive intestinal disorder characterized by a drastic reduction or absence of sucrase and isomaltase activities. Previous studies have indicated that single mutations underlie individual phenotypes of the disease. We investigated whether compound heterozygous mutations, observed in some patients, have a role in disease pathogenesis. METHODS: We introduced mutations into the SI complementary DNA that resulted in the amino acid substitutions V577G and G1073D (heterozygous mutations found in one group of patients) or C1229Y and F1745C (heterozygous mutations found in another group). The mutant genes were expressed transiently, alone or in combination, in COS cells and the effects were assessed at the protein, structural, and subcellular levels. RESULTS: The mutants SI-V577G, SI-G1073D, and SI-F1745C were misfolded and could not exit the endoplasmic reticulum, whereas SI-C1229Y was transported only to the Golgi apparatus. Co-expression of mutants found on each SI allele in patients did not alter the protein's biosynthetic features or improve its enzymatic activity. Importantly, the mutations C1229Y and F1745C, which lie in the sucrase domains of SI, prevented its targeting to the cell's apical membrane but did not affect protein folding or isomaltase activity. CONCLUSIONS: Compound heterozygosity is a novel pathogenic mechanism of congenital SI deficiency. The effects of mutations in the sucrase domain of SIC1229Y and SIF1745C indicate the importance of a direct interaction between isomaltase and sucrose and the role of sucrose as an intermolecular chaperone in the intracellular transport of SI.

Traffic Routes and Signals for the Tonoplast

Tonoplast, the membrane delimiting plant vacuoles, regulates ion, water and nutrient movement between the cytosol and the vacuolar lumen through the activity of its membrane proteins. Correct traffic of proteins from the endoplasmic reticulum (ER) to the tonoplast requires (i) approval by the ER quality control, (ii) motifs for exit from the ER and (iii) motifs that promote sorting to the tonoplast. Recent evidence suggests that this traffic follows different pathways that are protein-specific and could also reflect vacuole specialization for lytic or storage function. The routes can be distinguished based on their sensitivity to drugs such as brefeldin A and C834 as well as using mutant plants that are defective in adaptor proteins of vesicle coats, or dominant-negative mutants of Rab GTPases.

Sportvereine als Interessenorganisationen?! Ziel-Interessen-Divergenzen und ihre Auswirkungen

Einleitung: Freiwillige Sportorganisationen wie Sportvereine sind als Interessenorganisationen zu charakterisieren, deren primärer Organisationszweck sich auf die Vertretung der Interessen ihrer Mitglieder bezieht (Nagel, 2006). Mit dieser Interessenvertretungsfunktion wird gewährleistet, dass die Vereinsziele an die Mitgliederinteressen rückgebunden bleiben und Ziel-Interessen-Kongruenz herrscht (Schimank, 2005). Die Beobachtungen der Ver-einsrealität weisen jedoch darauf hin, dass die Ziele der Vereine oftmals von den Interessen ihrer Mitglieder abweichen und im Widerspruch zueinander stehen (Baur & Burrmann, 2003; Heinemann, 2004). Vor diesem Problemhintergrund ist zu fragen: Inwiefern stimmen die Vereinsziele mit den Mitgliederinteressen überein? Und für den Fall von Ziel-Interessen-Divergenzen, welche Auswirkungen ergeben sich daraus für die Vereine? Theoretisch-methodischer Ansatz: Für die theoriegeleite Beantwortung der Fragestellungen wurde auf Grundlage einer akteurtheoretischen Kon-zeptualisierung von Vereinen als Interessenorganisationen (Nagel, 2006; Schimank, 2007) ein strukturell-individualistisches Mehr-Ebenen-Modell entwickelt, dass zum einen das Verhältnis von Vereinszielen (Vereins-ebene) und Mitgliederinteressen (Mitgliederebene) und damit die Genese von Ziel-Interessen-Divergenzen erklärt. Zum anderen liefert das Modell eine Erklärungsgrundlage, welche Auswirkungen Divergenzen (struktu-relle Vereinssituation) auf die Mitglieder haben, d.h. wie die Mitglieder auf bestehende Divergenzen reagieren (individuelle Mitgliederhandlung). Die erforderlichen Vereins- und Mitgliederdaten wurden im Rahmen zweier Teilstudien erfasst, bei denen in erster Linie quantitative Erhebungs- und Auswertungsverfahren zum Einsatz kamen. Die erste Teilstudie wurde im Fürstentum Liechtenstein zur Analyse der Ziel-Interessen-Übereinstimmung durchgeführt, wobei hierzu die Präsidenten von 17 Vereinen und 481 Mitglieder schriftlich befragt wurden. In der zweiten Teilstudie wurde im Schweizer Turnverein Länggasse Bern mit 199 Mitgliedern eine schriftliche Befragung durchgeführt, um die Auswirkungen von Divergenzen zu analysieren. Zur Erfassung des Ausmasses von Ziel-Interessen-Divergenzen wurde eine Vergleichsprüfung der Vereinsziele und Mitgliederinteressen durchgeführt. Die Liechtensteinischen Vereinspräsidenten und Vereinsmitglieder mussten diesbezüglich die Bedeutung von 23 verschiedenen Items eines entwickelten Ziel-/Interessen-Fragekataloges einschätzen und über den betragsmässigen Bedeutungsunterschied konnte das quantitative Divergenzmass bestimmt werden. Um die Frage nach den Auswirkungen zu klären, hatten die Mitglieder des Schweizer Turnvereins Länggase Bern Aussagen über ihre Reaktionen auf bestehende Divergenzen entlang einer konzipierten Handlungstypologie (exit, voice, loyalty, neglect) zu geben. Ergebnisse: Die Befunde der Vergleichsanalyse zeigen, dass in allen untersuchten Vereinen Ziel-Interessen-Divergenzen in unterschiedlichem Ausmaß existieren. Bei einem Drittel der Vereine bestehen mittlere Divergenzen und in zwei Drittel sind größere Divergenzen zu beobachten. Divergenzen bestehen dabei vor allem hinsichtlich des Brei-tensports (v.a. Erweiterung des Sportangebots), der Vereinsentwicklung (v.a. Öffnen für neue Entwicklungen) und der Geselligkeit (v.a. aussersportliches Angebot, Wahrung der Vereinstradition). Die Analyse der Auswirkungen zeigt, dass geringe und mittelstarke Divergenzen in erster Linie zu konstruktiven Reaktionen führen. Die Mitglieder machen dabei die Vereinsführung auf diese Situation aufmerksam (voice), indem sie das Problem ansprechen und Vorschläge zur Problemlösung unterbreiten. Oder sie haben aus Grün-den der Vereinsverbundenheit (loyalty) die Hoffnung und das Vertrauen, dass die Vereinsführung ohne ihr Eingreifen das Problem löst. Wenn aber großen Divergenzen existieren, die sich für die Vereine zu einem gra-vierenden Problem entwickeln, tendieren die Mitglieder hingegen verstärkt zu destruktiven Reaktionen, die sich durch Gleichgültigkeit und Desinteresse am Vereinsgeschehen (neglect) äussern, indem die Mitglieder zukünftig nicht mehr auf Vereinsanlässe gehen. Oder sie wählen die Option des Rückzugs und Austritts (exit), indem sie ihr Vereinsengagement aufgeben oder im Extremfall aus der Abteilung oder dem Verein austreten. Diskussion: In der Vereinsrealität stellen Ziel-Interessen-Divergenzen offenbar eher die Norm als die Ausnahme dar, so dass die Vereinsziele nur teilweise an die Mitgliederinteressen rückgebunden sind. Allerdings sind Divergenzen nicht grundsätzlich als Problem zu interpretieren, sondern sind vielmehr in Abhängigkeit ihrer Intensität zu beurtei-len. Diesbezüglich dürften Vereine geringfügig bis mittelmässig ausgeprägte Divergenzsituationen im laufenden Vereinsgeschehen bis zu einem gewissen Grad relativ gut aushalten und aufarbeiten können, weil die Mitglie-der in diesem Fall zu einem konstruktiven Umgang tendieren, die eine Wiederherstellung von Ziel-Interessen-Kongruenz begünstigt. Demgegenüber können sich aber grosse Divergenzen zu einem ernsthaften Problem für Vereine entfalten, weil die Mitglieder in diesem Fall zu destruktiven Reaktionen neigen, die sich negativ auf die Vereinsentwicklung auswirken dürfte. Literatur Baur, J. & Burrmann, U. (2003). Konflikte in Sportvereinen. In J. Baur & S. Braun (Hrsg.), Integrationsleistungen von Sport-vereinen als Freiwilligenorganisationen (S. 331-370). Aachen: Meyer & Meyer. Nagel, S. (2006). Sportvereine im Wandel. Akteurtheoretische Analysen zur Entwicklung von Sportvereinen. Schorndorf: Hofmann. Nagel, S. (2007). Akteurtheoretische Analyse der Sportvereinsentwicklung. Ein theoretisch-methodischer Bezugsrahmen. Sportwissenschaft, 37 (2), 186-201. Schimank, U. (2005). Der Vereinssport in der Organisationsgesellschaft: organisationssoziologische Perspektiven auf ein spannungsreiches Verhältnis. In T. Alkemeyer, B. Rigauer & G. Sobiech (Hrsg.), Organisationsentwicklungen und De-Institutionalisierungsprozesse im Sport (S. 21-44). Schorndorf: Hofmann. Schimank, U. (2007). Handeln und Strukturen. Einführung in die akteurtheoretische Soziologie. Weinheim: Juventa Verlag.

Mammalian iron transporters: Families SLC11 and SLC40

This review is focused on the mammalian SLC11 and SLC40 families and their roles in iron homeostasis. The SLC11 family is composed of two members, SLC11A1 and SLC11A2. SLC11A1 is expressed in the lysosomal compartment of macrophages and in the tertiary granules of neutrophils, playing a key role in innate resistance against infection by intracellular microbes. SLC11A2 is a key player in iron metabolism and is ubiquitously expressed, most notably in the proximal duodenum, immature erythroid cells, brain, placenta and kidney. Intestinal iron absorption is mediated by SLC11A2 at the apical membrane of enterocytes, followed by basolateral exit via SLC40A1. To meet the daily requirement for iron, approximately 80% of the iron comes from the breakdown of hemoglobin following macrophage phagocytosis of senescent erythrocytes (iron recycling). Both SLC11A1 and SLC11A2 play an important role in macrophage iron recycling. SLC11A2 also transports iron into the cytosol across the membrane of endocytotic vesicles of the transferrin receptor-cycle. SLC40A1 is the sole member of the SLC40 family and is involved in the only cellular iron efflux mechanism described. SLC40A1 is highly expressed in several tissues and cells that play a critical role in body iron homeostasis. The signaling pathways that regulate SLC11A2 and SLC40A1 expression at transcriptional, post-transcriptional and post-translational levels are discussed. The roles of SLC11A2 and/or SLC40A1 in iron-associated disorders such as hemochromatosis, neurodegenerative diseases, and breast cancer are also summarized.

THE SOLAR WIND AS A POSSIBLE SOURCE OF FAST TEMPORAL VARIATIONS OF THE HELIOSPHERIC RIBBON

We present a possible source of pickup ions (PUIs) the ribbon observed by the Interstellar Boundary EXplorer (IBEX). We suggest that a gyrating solar wind and PUIs in the ramp and in the near downstream region of the termination shock (TS) could provide a significant source of energetic neutral atoms (ENAs) in the ribbon. A fraction of the solar wind and PUIs are reflected and energized during the first contact with the TS. Some of the solar wind may be reflected propagating toward the Sun but most of the solar wind ions form a gyrating beam-like distribution that persists until it is fully thermalized further downstream. Depending on the strength of the shock, these gyrating distributions can exist for many gyration periods until they are scattered/thermalized due to wave-particle interactions at the TS and downstream in the heliosheath. During this time, ENAs can be produced by charge exchange of interstellar neutral atoms with the gyrating ions. In order to determine the flux of energetic ions, we estimate the solar wind flux at the TS using pressure estimates inferred from in situ measurements. Assuming an average path length in the radial direction of the order of a few AU before the distribution of gyrating ions is thermalized, one can explain a significant fraction of the intensity of ENAs in the ribbon observed by IBEX. With a localized source and such a short integration path, this model would also allow fast time variations of the ENA flux.