The AMS-02 Experiment and the Dark Matter Search

AMS-02 is running after great scientific goals since one year and a half: a final setting up for dark matter searches has been achieved, allowing to study the so important antiparticle to particle ratios, which will probably be the first dark matter signals ever corroborated. Even if primary cosmic rays fluxes are subjected to a lot of uncertainties sources, some statements can be done and have been written down about dark matter properties: DM should be a heavy Majorana fermion or Spin 0 or 1 boson, with a mass from about 1 TeV to 10 TeV - unveiling a new TeV-ish search age - which could be able to originate antiparticle fluxes enhancements at high energies, both for positrons and antiprotons. All the observations, direct and indirect, point to these new paradigms or can be traced back to them quite easily. These enhancements perfectly fall into the research window of AMS-02, allowing the experiment to attack each today credible theory. Also an investigation of the Sommerfeld effect-associated dark boson will be possible, in terms of antiparticle to particle ratios substructures. The first great AMS-02 measurement is the positron fraction: an official paper is going to be submitted in few months, where the correct behavior of the apparatus will be reviewed and the full positron fraction rate will be analyzed up to 200 GeV. In this concern, one of the objectives of this work is to test the AMS-02 capability and versatility in doing these dark matter researches, thanks to an orbital temporal (and geomagnetic) stability. The goal has been accomplished: the experiment is very stable in time, so that the temporal error associated to the positron fraction measurement is compatible with zero, offering a beyond belief opportunity to measure CR antiparticle to particle ratios.

Virus oncogeni a dna in tumori umani: studio delle infezioni da papillomavirus e poliomavirus in neoplasie di diversa origine.

I virus tumorali inducono oncogenesi nel loro ospite naturale o in sistemi animali sperimentali, manipolando diverse vie cellulari. Ad oggi, sono stati identificati sette virus capaci di causare specifici tumori umani. Inoltre HPV, JCV ed SV40, sono stati associati con un grande numero di tumori umani in sedi corporee non convenzionali, ma, nonostante molti anni di ricerca, nessuna eziologia virale è stata ancora confermata. Lo scopo di questo studio è stato di valutare la presenza ed il significato sia di JCV ed SV40 in tumori ossei umani, e di HPV nel carcinoma della mammella (BC), galattoforectomie (GF), secrezioni mammarie patologiche (ND) e glioblastoma multiforme (GBM). Tecniche di biologia molecolare sono state impiegate per esaminare campioni di tessuto tumorale di 70 tumori ossei (20 osteosarcomi [OS], 20 tumori a cellule giganti [TCG], 30 condrosarcomi [CS]), 168 BCs , 30 GFs, 59 GBM e 30 campioni di ND. Il genoma di SV40 e JCV è stato trovato nel 70% dei CS + 20% degli OS, e nel 13% dei CS +10% dei TCG, rispettivamente. Il DNA di HPV è stato rilevato nel 30% dei pazienti con BC, nel 27% dei campioni GF e nel 13% dei NDs. HPV16 è stato il genotipo maggiormente osservato in tutti questi campioni, seguito da HPV18 e HPV35. Inoltre, il DNA di HPV è stato trovato nel 22% dei pazienti con GBM, in questo tumore HPV6 era il tipo più frequentemente rilevato, seguito da HPV16. L’ ISH ha mostrato che il DNA di HPV è situato all’interno di cellule tumorali mammarie e di GBM. I nostri risultati suggeriscono un possibile ruolo di JCV, SV40 e HPV in questi tumori, se non come induttori come promotori del processo neoplastico, tuttavia diversi criteri devono ancora essere soddisfatti prima di chiarirne il ruolo.

Pathogenetische Bedeutung der Glutathionperoxidase-1 in der arteriellen Gefäßwand

Die antioxidative Aktivität des Enzyms Glutathionperoxidase-1 (GPx-1) schützt vor Atherosklerose und ihren Folgeerkrankungen. In einer Vorstudie konnten wir zeigen, dass der Mangel an GPx-1 die Atheroskleroseentwicklung in Apolipoprotein E defizienten (ApoE-/-) Mäusen beschleunigt und modifiziert. Allerdings sind die Verteilung der GPx-1 in atherosklerotischen Läsionen und die Mechanismen für den erhöhten Makrophagengehalt in der Läsion noch nicht geklärt. Deshalb haben wir (1) die in-situ Expression der GPx-Isoformen in atherosklerotischen Läsionen von GPx-1-/-ApoE-/- und ApoE-/- Mäusen und (2) den Einfluss der GPx-1 Defizienz auf die Schaumzellbildung und Proliferation der Peritonealmakrophagen in ApoE-/- Mäusen untersucht. Die GPx-1-/-ApoE-/- und ApoE-/- Weibchen wurden für 6 und 12 Wochen auf einer atherogenen „Western-type“ Diät gehalten. Die in situ-Hybridisierung zeigte, dass die verschiedenen Isoformen der GPx (GPx-1, GPx-3, GPx-4) vorwiegend in Makrophagen, nicht jedoch in glatten Muskelzellen der atherosklerotischen Läsionen von ApoE-/- Mäusen exprimiert wurden. Für die in vitro Untersuchungen wurden 5 Monate alte, GPx-1 defiziente und Wildtyp-Mäuse, gehalten auf Normaldiät, verwendet. Die Öl-Rot-O Färbung zeigte, dass die GPx-1 Defizienz die OxLDL (oxidiertes LDL) - und E-LDL (enzymatisch modifiziertes LDL) - induzierte Schaumzellbildung förderte. Darüber hinaus war die OxLDL-induzierte Cholesterinakkumulation (zellulärer Cholesterinester/ Cholesterin-Gehalt) in GPx-1 defizienten Makrophagen verstärkt, sodass ein Mangel an GPx-1 die Aufnahme von OxLDL durch Monozyten und damit die Umwandlung in Schaumzellen beschleunigt. Hinsichtlich der Proliferation zeigte sich, dass MCSF (Macrophage Colony-Stimulating Facotr) ein stärkerer Stimulus als OxLDL ist. Ein Mangel an GPx-1 fördert die Proliferation zusätzlich. Daran ist die ERK1/2 (extracellular-signal regulated kinase 1/2) - Kaskade beteiligt, denn es wurde eine schnelle Phosphorylierung der ERK1/2-Kaskade durch MCSF und/oder OxLDL nachgewiesen. Entsprechend reduzieren ERK1/2-Inhibitoren die proliferative Aktivität der Makrophagen. Die Hemmung der p38-MAPK (p38 mitogen-activated protein kinase) führt zur vermehrten Proliferation und bei gleichzeitig verringerter Caspase-3/7 Aktivität der Makrophagen unabhängig von der Expression der GPx-1. Ein Mangel an GPx-1 hat auch keinen Einfluss auf die MCSF-vermittelte Aktivierung der p38-MAPK und JNK (c-Jun N-terminal kinase). Zusammenfassend läßt sich feststellen, dass die GPx-1-Defizienz einen signifikanten Einfluss auf die Schaumzellbildung und Proliferation von Makrophagen hat, was zur Beschleunigung der Atherosklerose und zu vermehrter Zellularität der entstehenden atherosklerotischen Läsionen führt. Die Proliferation wird über den ERK1/2 Signal-transduktionsweg positiv und über den p38-MAPK Weg negativ reguliert, wobei die ERK1/2-Kaskade empfindlich gegenüber oxidativem Stress bei GPx-1-Defizienz ist.

Expression patterns of neurexin-1 and neuroligins in brain and retina of the chick embryo: Neuroligin-3 is absent in retina

Neuroligins (NLs) constitute a family of cell-surface proteins that interact with neurexins (beta-Nxs), another class of neuronal cell-surface proteins, one of each class functioning together in synapse formation. The localization of the various neurexins and neuroligins, however, has not yet been clarified in chicken. Therefore, we studied the expression patterns of neurexin-1 (Nx-1) and neuroligin-1 and -3 during embryonic development of the chick retina and brain by reverse-transcriptase polymerase chain reaction (RT-PCR) and in situ hybridization (ISH). While neurexin-1 increased continuously in both brain and retina, the expression of both neuroligins was more variable. As shown by ISH, Nx-1 is expressed in the inner half retina along with differentiation of ganglion and amacrine cells. Transcripts of NL-1 were detected as early as day 4 and increased with the maturation of the different brain regions. In different brain regions, NL-1 showed a different time regulation. Remarkably, neuroligin-3 was entirely absent in retina. This study indicates that synaptogenetic processes in brain and retina use different molecular machineries, whereby the neuroligins might represent the more distinctly regulated part of the neurexin-neuroligin complexes. Noticeably, NL-3 does not seem to be involved in the making of retinal synapses.

Distribution of the glutamate transporters GLT-1 (SLC1A2) and GLAST (SLC1A3) in peripheral organs

The glutamate transporters GLT-1 and GLAST are widely expressed in astrocytes in the brain where they fulfill important functions during glutamatergic neurotransmission. The present study examines their distribution in peripheral organs using in situ hybridization (ISH) and immunocytochemistry. GLAST was found to be more widely distributed than GLT-1. GLAST was expressed primarily in epithelial cells, cells of the macrophage-lineage, lymphocytes, fat cells, interstitial cells, and salivary gland acini. GLT-1 was primarily expressed in glandular tissue, including mammary gland, lacrimal gland, and ducts and acini in salivary glands, but also by perivenous hepatocytes and follicular dendritic cells in spleen and lymph nodes. The findings demonstrate that, although expressed by the same cells in the brain, these two glutamate transporters have different distribution patterns in peripheral tissues and that they fulfill glutamate transport functions apart from glutamatergic neurotransmission in these areas.

Ventricular-arterial coupling in a rat model of reduced arterial compliance provoked by hypervitaminosis D and nicotine

The vitamin D(3) and nicotine (VDN) model is one of isolated systolic hypertension (ISH) in which arterial calcification raises arterial stiffness and vascular impedance. The effects of VDN treatment on arterial and cardiac hemodynamics have been investigated; however, a complete analysis of ventricular-arterial interaction is lacking. Wistar rats were treated with VDN (VDN group, n = 9), and a control group (n = 10) was included without the VDN. At week 8, invasive indexes of cardiac function were obtained using a conductance catheter. Simultaneously, aortic pressure and flow were measured to derive vascular impedance and characterize ventricular-vascular interaction. VDN caused significant increases in systolic (138 +/- 6 vs. 116 +/- 13 mmHg, P < 0.01) and pulse (42 +/- 10 vs. 26 +/- 4 mmHg, P < 0.01) pressures with respect to control. Total arterial compliance decreased (0.12 +/- 0.08 vs. 0.21 +/- 0.04 ml/mmHg in control, P < 0.05), and pulse wave velocity increased significantly (8.8 +/- 2.5 vs. 5.1 +/- 2.0 m/s in control, P < 0.05). The arterial elastance and end-systolic elastance rose significantly in the VDN group (P < 0.05). Wave reflection was augmented in the VDN group, as reflected by the increase in the wave reflection coefficient (0.63 +/- 0.06 vs. 0.52 +/- 0.05 in control, P < 0.05) and the amplitude of the reflected pressure wave (13.3 +/- 3.1 vs. 8.4 +/- 1.0 mmHg in control, P < 0.05). We studied ventricular-arterial coupling in a VDN-induced rat model of reduced arterial compliance. The VDN treatment led to development of ISH and provoked alterations in cardiac function, arterial impedance, arterial function, and ventricular-arterial interaction, which in many aspects are similar to effects of an aged and stiffened arterial tree.

Effects of an aging vascular model on healthy and diseased hearts

The vitamin D(3) and nicotine (VDN) model is a model of isolated systolic hypertension (ISH) due to arterial calcification raising arterial stiffness and vascular impedance similar to an aged and stiffened arterial tree. We therefore analyzed the impact of this aging model on normal and diseased hearts with myocardial infarction (MI). Wistar rats were treated with VDN (n = 9), subjected to MI by coronary ligation (n = 10), or subjected to a combination of both MI and VDN treatment (VDN/MI, n = 14). A sham-treated group served as control (Ctrl, n = 10). Transthoracic echocardiography was performed every 2 wk, whereas invasive indexes were obtained at week 8 before death. Calcium, collagen, and protein contents were measured in the heart and the aorta. Systolic blood pressure, pulse pressure, thoracic aortic calcium, and end-systolic elastance as an index of myocardial contractility were highest in the aging model group compared with MI and Ctrl groups (P(VDN) < 0.05, 2-way ANOVA). Left ventricular wall stress and brain natriuretic peptide (P(VDNxMI) = not significant) were highest, while ejection fraction, stroke volume, and cardiac output were lowest in the combined group versus all other groups (P(VDNxMI) < 0.05). The combination of ISH due to this aging model and MI demonstrates significant alterations in cardiac function. This model mimics several clinical phenomena of cardiovascular aging and may thus serve to further study novel therapies.

Der shṿartser bukh : di oyṭorizirṭe Idishe iberzetsung fun "The Jews in the Eastern war zone" (Di idn in di milḥome-gegenden fun Mizreḥ-Eyropa)

fun Ṿilyam Poyzniaḳ. Miṭ der erloybnis fun der "Ameriḳan Dʹzshuʾish Ḳomiṭe"

Seder ha-limud le-lel Shavuʿot

mesudar ... u-meduyaḳ ... me-et Ṿolf ... Ish Haydenhaym

Seder ha-haggada le-lel shimmurim : meduik hetev u-mesudar yafe u-meturgam ashkenazit

me'et Wolf ... ish Haydnhaym

Sefer Ḳerovot hu maḥazor : mesudar bi-shelemut ha-sidur u-meduyaḳ be-takhlit ha-diyuḳ

me-iti Ṿolf b.R. Shimʿon Dov ish Haydenhaym