Evidence for the Galactic X-ray Bulge II

A mosaic of 5 \ros~PSPC pointed observations in the Galactic plane ($l\sim25^{\circ}$) reveals X-ray shadows in the $0.5-2.0$ keV band cast by distant molecular clouds. The observed on-cloud and off-cloud X-ray fluxes indicate that $\sim15$% and $\sim37$% of the diffuse X-ray background in this direction in the \tq~keV and 1.5 keV bands, respectively, originates behind the molecular gas which is located at $\sim$3 kpc from the Sun. The implication of the derived background X-ray flux beyond the absorbing molecular cloud is consistent with, and lends further support to recent observations of a Galactic X-ray bulge.Comment: 19 pages, 5 figures, 2 table

Importance of the loading factor in transport CO2 emissions

This paper is focusing on the influence of the loading factor on CO2 emissions, from freight and passengers. A common approach in economics to relate greenhouse gas (GHG) emissions to economic activity is the ASIF model (Unander & Schipper 2000). However, this model has been elaborated for all economic sectors, and it doesn’t take into account the vehicle load factor for the calculation of transport emissions. The objective of this paper is to include the loading factor into the ASIF approach. First, we will include this loading factor into the ASIF equation, aggregating step by step from trip level to macro level; loading will appear as a result of empty running, vehicle capacity and occupancy rate (section 2). Then section 3 will analyse the relationship between loading factor and energy consumption, per type of vehicle. Section 4 will focus on issues concerning freight, as well as section 5 for passengers. The examples will be mainly taken from road transport, which causes most of transport CO2 emissions. Then our conclusion will draw attention on data needs and policy implications

Kombinirani učinci smjenskog rada i faktora okoline (vrućina, buka, toksični agensi)

The paper deals with the results of studies or discussions concerning the problem of nightwork combined with other adverse working conditions. Special emphasis is laid on the untoward effect of high temperature during nightwork, as well as on noise and exposure to chemicals. It is shown that there is no substantial influence of heat stress on the circadian rhythm of adrenaline excretion under sitting working conditions with the subject performing a difficult mental task at warm climates up to 30 °C BET. Shiftwork and noise induce independent different effects which can be explained in terms of activation for shiftwork and in terms of tension for noise. The combination of both adverse exposures is therefore partly subtractive but partly additive as night work and noise negatively affect daysleep. Practical experience in the field of combined effects of shiftwork and chemical agents is lacking, but theoretical speculations lead to the conclusion that there may exist a time of day dependence of some chemicals, used at workplaces.U radu su prikazani rezultati istraživanja i iznesena je teorijska rasprava o problemu smjenskog rada povezanim s drugim nepovoljnim uvjetima rada. Naročito je naglašeno moguće negativno djelovanje visoke temperature za vrijeme smjenskog rada, kao i utjecaj buke i izloženost kemikalijama. Nađeno je da nema značajnog utjecaja toplinskog stresa na dnevni ritam izlučivanja adrenalina pri sjedećem teškom mentalnom radu sve dok temperatura ne pređe 30 ° BET. Smjenski rad i buka imaju neovisno djelovanje koje se može razjasniti aktivnošću u smjenskom radu i napetošću uzrokovanom bukom. Stoga je djelovanje ovih dvaju negativnih utjecaja djelomično suprotno, a djelomično aditivna, budući da noćni rad i buka negativno utiču na san slijedećeg dana. Nedostaju iskustva o kombiniranom djelovanju smjenskog rada i kemijskih spojeva u radnoj okolini, no teorijske pretpostavke dovode do zaključka da bi mogle postojati razlike u toksičnosti pojedinih kemikalija s obzirom na doba dana

Forever Young: High Chromospheric Activity in M subdwarfs

We present spectroscopic observations of two halo M subdwarfs which have H alpha emission lines. We show that in both cases close companions are the most likely cause of the chromospheric activity in these old, metal-poor stars. We argue that Gl 781 A's unseen companion is most likely a cool helium white dwarf. Gl 455 is a near-equal-mass M subdwarf (sdM) system. Gl 781 A is rapidly rotating with v sin i = 30 km/s. The properties of the chromospheres and X-ray coronae of these systems are compared to M dwarfs with emission (dMe). The X-ray hardness ratios and optical chromospheric lines emission ratios are consistent with those seen in dMe stars. Comparison to active near-solar metallicity stars indicates that despite their low metallicity ([m/H] = -1/2), the sdMe stars are roughly as active in both X-rays and chromospheric emission. Measured by L_X/L_bol, the activity level of Gl 781 A is no more than a factor of 2.5 subluminous with respect to near-solar metallicity stars.Comment: 16 pages including 1 figure, AASTeX, to appear in May 1998 A.

Differential effects of selective inhibitors targeting the PI3K/AKT/mTOR pathway in acute lymphoblastic leukemia

Purpose: Aberrant PI3K/AKT/mTOR signaling has been linked to oncogenesis and therapy resistance in various malignancies including leukemias. In Philadelphia chromosome (Ph) positive leukemias, activation of PI3K by dysregulated BCR-ABL tyrosine kinase (TK) contributes to the pathogenesis and development of resistance to ABL-TK inhibitors (TKI). The PI3K pathway thus is an attractive therapeutic target in BCR-ABL positive leukemias, but its role in BCR-ABL negative ALL is conjectural. Moreover, the functional contribution of individual components of the PI3K pathway in ALL has not been established. Experimental design: We compared the activity of the ATP-competitive pan-PI3K inhibitor NVP-BKM120, the allosteric mTORC1 inhibitor RAD001, the ATP-competitive dual PI3K/mTORC1/C2 inhibitors NVP-BEZ235 and NVP-BGT226 and the combined mTORC1 and mTORC2 inhibitors Torin 1, PP242 and KU-0063794 using long-term cultures of ALL cells (ALL-LTC) from patients with B-precursor ALL that expressed the BCR-ABL or TEL-ABL oncoproteins or were BCR-ABL negative. Results: Dual PI3K/mTOR inhibitors profoundly inhibited growth and survival of ALL cells irrespective of their genetic subtype and their responsiveness to ABL-TKI. Combined suppression of PI3K, mTORC1 and mTORC2 displayed greater antileukemic activity than selective inhibitors of PI3K, mTORC1 or mTORC1 and mTORC2. Conclusions: Inhibition of the PI3K/mTOR pathway is a promising therapeutic approach in patients with ALL. Greater antileukemic activity of dual PI3K/mTORC1/C2 inhibitors appears to be due to the redundant function of PI3K and mTOR. Clinical trials examining dual PI3K/mTORC1/C2 inhibitors in patients with B-precursor ALL are warranted, and should not be restricted to particular genetic subtypes

Discovery of 14-3-3 PPI Stabilizers by Extension of an Amidine-Substituted Thiophene Fragment

Protein-protein interaction (PPI) modulation is a promising approach in drug discovery with the potential to expand the 'druggable' proteome and develop new therapeutic strategies. While there have been significant advancements in methodologies for developing PPI inhibitors, there is a relative scarcity of literature describing the 'bottom-up' development of PPI stabilizers (Molecular Glues). The hub protein 14-3-3 and its interactome provide an excellent platform for exploring conceptual approaches to PPI modulation, including evolution of chemical matter for Molecular Glues. In this study, we employed a fragment extension strategy to discover stabilizers for the complex of 14-3-3 protein and an Estrogen Receptor alpha-derived peptide (ERα). A focused library of analogues derived from an amidine-substituted thiophene fragment enhanced the affinity of the 14-3-3/ERα complex up to 6.2-fold. Structure-activity relationship (SAR) analysis underscored the importance of the newly added, aromatic side chain with a certain degree of rigidity. X-ray structural analysis revealed a unique intermolecular π-π stacking binding mode of the most active analogues, resulting in the simultaneous binding of two molecules to the PPI binding pocket. Notably, analogue 11 displayed selective stabilization of the 14-3-3/ERα complex.</p

Inhibition of HIV-1 replication by small interfering RNAs directed against Glioma Pathogenesis Related Protein (GliPR) expression

Background: Previously, we showed that glioma pathogenesis related protein (GliPR) is induced in CEM T cells upon HIV-1 infection in vitro. To examine whether GliPR plays a role as HIV dependency factor (HDF), we tested the effect of GliPR suppression by siRNA on HIV-1 replication. Results: Induction of GliPR expression by HIV-1 was confirmed in P4-CCR5 cells. When GliPR was suppressed by siRNA, HIV-1 replication was significantly reduced as measured by HIV-1 transcript levels, HIV-1 p24 protein levels, and HIV-1 LTR-driven reporter gene expression, suggesting that GliPR is a cellular co-factor of HIV-1. Microarray analysis of uninfected HeLa cells following knockdown of GliPR revealed, among a multitude of gene expression alterations, a down-regulation of syndecan-1, syndecan-2, protein kinase C alpha (PRKCA), the catalytic subunit beta of cAMP-dependent protein kinase (PRKACB), nuclear receptor co-activator 3 (NCOA3), and cell surface protein CD59 (protectin), all genes having relevance for HIV-1 pathology. Conclusions: The up-regulation of GliPR by HIV-1 and the early significant inhibition of HIV-1 replication mediated by knockdown of GliPR reveal GliPR as an important HIV-1 dependency factor (HDF), which may be exploited for HIV-1 inhibition

Magnetoelastic coupling and ferromagnetic-type in-gap spin excitations in multiferroic α-Cu2V2O7

We investigate magnetoelectric coupling and low-energy magnetic excitations in multiferroic α-Cu2V2O7 by detailed thermal expansion, magnetostriction, specific heat and magnetization measurements in magnetic fields up to 15 T and by high-field/high-frequency electron spin resonance studies. Our data show negative thermal expansion in the temperature range ≤200 K under study. Well-developed anomalies associated with the onset of multiferroic order (canted antiferromagnetism with a significant magnetic moment and ferroelectricity) imply pronounced coupling to the structure. We detect anomalous entropy changes in the temperature regime up to ∼80 K which significantly exceed the spin entropy. Failure of Grüneisen scaling further confirms that several dominant ordering phenomena are concomitantly driving the multiferroic order. By applying external magnetic fields, anomalies in the thermal expansion and in the magnetization are separated. Noteworthy, the data clearly imply the development of a canted magnetic moment at temperatures above the structural anomaly. Low-field magnetostriction supports the scenario of exchange-striction driven multiferroicity. We observe low-energy magnetic excitations well below the antiferromagnetic gap, i.e., a ferromagnetic-type resonance branch associated with the canted magnetic moment arising from Dzyaloshinsii-Moriya (DM) interactions. The anisotropy parameter meV indicates a sizeable ratio of DM- and isotropic magnetic exchange

Client self-assessment in community aged care: A comparative study involving older Australians and their case managers

Self-assessment of support needs is a relatively new and under-researched phenomenon in domiciliary aged care. This article outlines the results of a comparative study focusing on whether a self-assessment approach assists clients to identify support needs and the degree to which self-assessed needs differ from an assessment conducted by community care professionals. A total of 48 older people and their case managers completed a needs assessment tool. Twenty-two semi-structured interviews were used to ascertain older people&rsquo;s views and preferences regarding the self-assessment process. The study suggests that while a co-assessment approach as outlined in this article has the potential to assist older people to gain a better understanding of their care needs as well as the assessment process and its ramifications, client self-assessment should be seen as part of a co-assessment process involving care professionals. Such a co-assessment process allows older people to gain a better understanding of their support needs and the wider community aged care context. The article suggests that a co-assessment process involving both clients and care professionals contains features that have the capacity to enhance domiciliary aged care