Ionization history of the cosmic plasma in the light of the recent CBI and future PLANCK data

The paper is devoted to the methods of determination of the cosmological parameters from recent CMB observations. We show that the more complex models of kinetics of recombination with a few "missing" parameters describing the recombination process provide better agreement between measured and expected characteristics of the CMB anisotropy. In particular, we consider the external sources of the Ly-{alpha} and Ly-{c} radiation and the model with the strong clustering of baryonic component. These factors can constrain the estimates of the cosmological parameters usually discussed. We demonstrate also that the measurements of polarization can improve these estimates and, for the precision expected for the PLANCK mission, allow to discriminate a wide class of models.Comment: 25 pages, 7 figures, extended and corrected after the referee report. Accepted in Ap

Lesson Learned Dari Kecelakaan Reaktor Nuklir Fukushima Daiichi Untuk Meningkatkan Mitigasi Reaktor Serba Guna Gerrit Augustinus Siwabessy (RSG-GAS)

Indonesia dengan wilayah geografi yang relatif sama dengan Jepang dan sangat dipengaruhi oleh pergerakan lempeng tektonik menyebabkan Indonesia rawan terhadap gempa tektonik, terlebih Serpong Kota Tangerang Selatan lokasi Reaktor Serba Guna - G.A. Siwabessy (RSG-GAS) berada tercatat dalam buku Katalog Gempabumi Signifikan dan Merusak Tahun 1821-2018, sebagai wilayah berisiko terdampak gempa. Berdasarkan hal tersebut, penelitian ini mengidentifikasi dan menganalisis upaya mitigasi yang dilakukan untuk mengurangi risiko ancaman bencana akibat kegagalan teknologi di RSG-GAS. Metode penelitian yang digunakan kualitatif dengan desain penelitian deskriptif eksploratif, mengeksplorasi fenomena baru dan mendeskripsikan sesuai pengamatan langsung dari data primer yang diperoleh melalui wawancara dengan narasumber, dan data sekunder melalui studi dokumen milik narasumber dan studi pustaka. Validasi data dilakukan dengan teknik triangulasi dengan melakukan investigasi data dari berbagai sumber yang di analisis sesuai dengan kerangka penelitian. Tindakan mitigasi sudah dilakukan sebelum desain disusun, tepatnya pada penentuan calon tapak sampai pada saat ini tahap operasi. Pemutakhiran evaluasi tapak reaktor dilakukan pada aspek kejadian eksternal (aspek kegempaan, kegunungapian, geoteknik, meteorologi dan hidrologi, ulah manusia, serta dispersi zat radioaktif). Pemutakhiran evaluasi tapak dari aspek kejadian eksternal menjadi pertimbangan dalam desain RSG-GAS berbasis mitigasi, termasuk simulasi station balckout yang telah dilakukan di RSG-GAS, untuk mengetahui kapasitas dan kerentanan RSG-GAS terhadap bahaya eksternal yang terjadi seperti di Fukushima Daiichi. Peraturan Perundang-undangan terkait desain mempertimbangkan bahaya eksternal seperti gempabumi dan bahaya lainnya juga sudah diundangkan. Untuk memperkuat kapasitas pemerintah dan pemangku kepentingan perlu dilakukan revisi Peraturan Pemerintah untuk mengatur tanggung jawab dan kewenangannya dalam penanggulangan kedaruratan nuklir untuk menjamin keselamatan masyarakat guna tercipta keamanan nasional

Meninges: from protective membrane to stem cell niche

Meninges are a three tissue membrane primarily known as coverings of the brain. More in depth studies on meningeal function and ultrastructure have recently changed the view of meninges as a merely protective membrane. Accurate evaluation of the anatomical distribution in the CNS reveals that meninges largely penetrate inside the neural tissue. Meninges enter the CNS by projecting between structures, in the stroma of choroid plexus and form the perivascular space (Virchow-Robin) of every parenchymal vessel. Thus, meninges may modulate most of the physiological and pathological events of the CNS throughout the life. Meninges are present since the very early embryonic stages of cortical development and appear to be necessary for normal corticogenesis and brain structures formation. In adulthood meninges contribute to neural tissue homeostasis by secreting several trophic factors including FGF2 and SDF-1. Recently, for the first time, we have identified the presence of a stem cell population with neural differentiation potential in meninges. In addition, we and other groups have further described the presence in meninges of injury responsive neural precursors. In this review we will give a comprehensive view of meninges and their multiple roles in the context of a functional network with the neural tissue. We will highlight the current literature on the developmental feature of meninges and their role in cortical development. Moreover, we will elucidate the anatomical distribution of the meninges and their trophic properties in adult CNS. Finally, we will emphasize recent evidences suggesting the potential role of meninges as stem cell niche harbouring endogenous precursors that can be activated by injury and are able to contribute to CNS parenchymal reaction

Consistency and diversity of spike dynamics in the neurons of bed nucleus of Stria Terminalis of the rat: a dynamic clamp study

Neurons display a high degree of variability and diversity in the expression and regulation of their voltage-dependent ionic channels. Under low level of synaptic background a number of physiologically distinct cell types can be identified in most brain areas that display different responses to standard forms of intracellular current stimulation. Nevertheless, it is not well understood how biophysically different neurons process synaptic inputs in natural conditions, i.e., when experiencing intense synaptic bombardment in vivo. While distinct cell types might process synaptic inputs into different patterns of action potentials representing specific "motifs'' of network activity, standard methods of electrophysiology are not well suited to resolve such questions. In the current paper we performed dynamic clamp experiments with simulated synaptic inputs that were presented to three types of neurons in the juxtacapsular bed nucleus of stria terminalis (jcBNST) of the rat. Our analysis on the temporal structure of firing showed that the three types of jcBNST neurons did not produce qualitatively different spike responses under identical patterns of input. However, we observed consistent, cell type dependent variations in the fine structure of firing, at the level of single spikes. At the millisecond resolution structure of firing we found high degree of diversity across the entire spectrum of neurons irrespective of their type. Additionally, we identified a new cell type with intrinsic oscillatory properties that produced a rhythmic and regular firing under synaptic stimulation that distinguishes it from the previously described jcBNST cell types. Our findings suggest a sophisticated, cell type dependent regulation of spike dynamics of neurons when experiencing a complex synaptic background. The high degree of their dynamical diversity has implications to their cooperative dynamics and synchronization

Long-term Swift and Mets\"ahovi monitoring of SDSS J164100.10+345452.7 reveals multi-wavelength correlated variability

We report on the first multi-wavelength Swift monitoring campaign performed on SDSS J164100.10+345452.7, a nearby narrow-line Seyfert 1 galaxy formerly known as radio quiet which was recently detected both in the radio (at 37 GHz) and in the $\gamma$-rays, which hints at the presence of a relativistic jet. During our 20-month Swift campaign, while pursuing the primary goal of assessing the baseline optical/UV and X-ray properties of J1641, we caught two radio flaring episodes, one each year. Our strictly simultaneous multi-wavelength data closely match the radio flare and allow us to unambiguously link the jetted radio emission of J1641. Indeed, for the X-ray spectra preceding and following the radio flare a simple absorbed power-law model is not an adequate description, and an extra absorption component is required. The average spectrum of J1641 can be best described by an absorbed power law model with a photon index $\Gamma=1.93\pm0.12$, modified by a partially covering neutral absorber with a covering fraction $f=0.91_{-0.03}^{+0.02}$. On the contrary, the X-ray spectrum closest to the radio flare does not require such extra absorber and is much harder ($\Gamma_{\rm flare} \sim 0.7\pm0.4$), thus implying the emergence of a further, harder spectral component. We interpret this as the jet emission emerging from a gap in the absorber. The fractional variability we derive in the optical/UV and X-ray bands are found to be lower than the typical values reported in the literature, since our observations of J1641 are dominated by the source being in a low state. Under the assumption that the origin of the 37 GHz radio flare is the emergence of a jet from an obscuring screen also observed in the X-rays, the derived total jet power is $P^{\rm tot}_{\rm jet}=3.5\times10^{42}$ erg s$^{-1}$, comparable to the lowest measured in the literature. [Abridged]Comment: Accepted for publication in Astronomy and Astrophysics (13 pages, 4 figures, 8 tables

The Synthesis of some B6 Vitamin Halophosphates

A series of new halo-derivates of pyridoxine-3-O- or 5’-0-phosphates and pyridoxal-3-O- or 5’-0-phosphates have been synthesized. In the reaction of partially protected pyridoxine and pyridoxal (3-5) with phosphorusoxychlo- ride in the presence of triethylamine, the following dichlorophosphates were obtained: 3,4’-0-isopropylidenepyridoxine-5’-0-dichlorophosphate (6), 4,5’-0- isobutilidenepyridoxine-3-O-dichlorophosphate (7), and monoethylacetal-3-O- dicholorophosphate (8). Dichlorophosphates 6-8 reacted with NaF under catalytic action of 18-crown-6-ether, giving the corresponding difluorophos- phates 14-16. The 3,4’-0-isopropyiidene pyridoxine-5’-0-difluorophosphate (14), 4’,5’-isobutilydene-3-0-difluoro-phosphate (15) and monoethylacetal-3-O-di- fluorophosphate (16), in the reaction with aniline, yielded the corresponding monofluorophosphates in the form of aniline salts (17-19). The direct fluor- ination of pyridoxal-5’-phosphate with dinitrofluorobenzene yielded pyridox- al-5’-0-monofluorophosphate (I) which was isolated as cyclohexylamine salt (2)

Pharmacological Modulators of Sphingolipid Metabolism for the Treatment of Cystic Fibrosis Lung Inflammation

Cystic Fibrosis (CF) lung disease is characterised by progressive chronic infection and inflammation of the airways. This prolonged airway inflammatory response leads to irreversible lung damage and fibrosis which is believed to be driven by two distinct, coordinated events: a) a defective cystic fibrosis transmembrane regulator (CFTR) causes airway surface dehydration and increased mucus viscosity leading to chronic colonization with Pseudomonas aeruginosa (P.aeruginosa) (Boucher, 2007); b) mutated CFTR triggers the generation of pro-inflammatory and chemotactic cytokines orchestrated by bronchial epithelial cells, independently of infection (Rubin, 2007; Elizur et al., 2008). The chemokine IL-8, abundantly expressed at sites of chronic inflammation, seems to play a major role in driving the formation of neutrophil (PMN)-rich exudates into the lung of CF patients (Khan et al., 1995; Noah et al., 1997; DiMango et al., 1998; Puchelle et al., 2001; Joseph et al., 2005; Perez et al., 2007). Therefore, reduction of the exaggerated production of IL-8 is key therapeutic target in CF. Anti-inflammatory drugs are an attractive therapeutic tool in CF aimed to decrease the rate of decline in lung function. However, the inherent complexity of the inflammatory response combined with the obvious dependency on this response to contain infection and the side effect profiles of common anti-inflammatories, have made identifying the most suitable therapy a major priority. Consensus is growing on sphingolipids (SLs) as novel targets to cure pulmonary disorders including CF, since modulation of cellular ceramide reduces lung inflammation (Lahiri and Futerman, 2007; Uhlig and Gulbins, 2008). The results in the area of ceramide and CF pathophysiology are very interesting, although contradicting due to the animal models used and methods of ceramide detection (Wojewodka , 2011). The accumulation of ceramide has been identified as one of the key regulators of inflammation in CF airways in different CFTR-/- mouse models (Teichgraber, 2008). On the contrary, decreased ceramide levels have been shown in CFTR ko mice (Guibault, 2008). The possible explanation for this discrepancy seems to be the special diet required for CFTR ko mice, that severely affects the concentration of SLs. Other possible causes, such as genetic determinants, could influence individual levels of SLs (Hicks, 2009). In a different study, no significant difference has been found in basal ceramide levels in immortalised CF bronchial epithelial cells and lung homogenate from CFTR ko mice compared to wild type cells and mice (Yu, 2009). Very importantly, ceramide has been demonstrated to accumulate in the lower airways of CF patients and to be positively associated with neutrophilic inflammation (Brodlie, 2010), supporting the hypothesis that reduction of ceramide may be a therapeutic target for CF lung inflammation. Extending our previous study (Dechecchi, 2008), we have recently demonstrated that the iminosugar N-butyldeoxynojirimycin (miglustat), an inhibitor of the first step in glycosphingolipid (GSL) biosynthesis, reducing the P.aeruginosa induced immunoreactive ceramide expression, produces an anti-inflammatory effect in human bronchial epithelial cells in vitro and down-regulates the neutrophil chemotaxis in murine lungs in vivo (Dechecchi, 2011). These findings strengthen the notion that the metabolism of SLs can be manipulated as a therapeutic option for CF lung disease. With regard to new treatments for CF lung pathology, miglustat deserves great attention since it restores CFTR function in respiratory and pancreatic cells in vitro (Norez, 2006; Dechecchi, 2008) and in CF mice (Lubamba, 2009) and produces an anti-inflammatory effect in vitro and in vivo Dechecchi, 2011). Notably, miglustat is a FDA-approved and EMA−designated orally bioavailable orphan drug, used in Europe and USA for the treatment of Gaucher disease and other GSL storage diseases. In this chapter we review the pre-clinical evidence on the anti-inflammatory effect of miglustat in comparative effectiveness studies with the SL inhibitor amitriptyline and the glucocorticoid (GC) dexamethasone. Importance will be placed on the efficacy of each anti-inflammatory molecule to balance between the anti-inflammatory activity and possible impairment of the host defence

Gestão conservacionista de solo e de água em escala de microbacia hidrográfica: estudo de caso.

bitstream/CNPT-2010/40705/1/p-do87.pd

Safety and dose modification for patients receiving niraparib

Background: Niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved in the United States and Europe for maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. In the pivotal ENGOT-OV16/NOVA trial, the dose reduction rate due to TEAE was 68.9%, and the discontinuation rate due to TEAE was 14.7%, including 3.3% due to thrombocytopenia. A retrospective analysis was performed to identify clinical parameters that predict dose reductions. Patients and methods: All analyses were performed on the safety population, comprising all patients who received at least one dose of study drug. Patients were analyzed according to the study drug consumed (ie, as treated). A predictive modeling method (decision trees) was used to identify important variables for predicting the likelihood of developing grade ≥3 thrombocytopenia within 30 days after the first dose of niraparib and determine cutoff points for chosen variables. Results: Following dose modification, 200 mg was the most commonly administered dose in the ENGOT-OV16/NOVA trial. Baseline platelet count and baseline body weight were identified as risk factors for increased incidence of grade ≥3 thrombocytopenia. Patients with a baseline body weight <77 kg or a baseline platelet count <150,000/μL in effect received an average daily dose approximating 200 mg (median = 207 mg) due to dose interruption and reduction. Progression-free survival in patients who were dose reduced to either 200 mg or 100 mg was consistent with that of patients who remained at the 300 mg starting dose. Conclusions: The analysis presented suggests that patients with baseline body weight of < 77 kg or baseline platelets of < 150,000/μL may benefit from a starting dose of 200 mg per day. (ClinicalTrials.gov ID: NCT01847274)