Linear modeling of possible mechanisms for parkinson tremor generation

The power of Parkinson tremor is expressed in terms of possibly changed frequency response functions between relevant variables in the neuromuscular system. The derivation starts out from a linear loopless equivalent model of mechanisms for general tremor generation. Hypothetical changes in this model from the substrate of the disease are indicated, and possible ones are inferred from literature about experiments on patients. The result indicates that in these patients tremor appears to have been generated in loops, which did not include the brain area which in surgery usually is inactivated. For some patients in the literature, these loops could involve muscle length receptors, the static sensitivity of which may have been enlarged by pathological brain activity

CD20 and CD19 targeted vectors induce minimal activation of resting B lymphocytes

B lymphocytes are an important cell population of the immune system. However, until recently it was not possible to transduce resting B lymphocytes with retro- or lentiviral vectors, making them unsusceptible for genetic manipulations by these vectors. Lately, we demonstrated that lentiviral vectors pseudotyped with modified measles virus (MV) glycoproteins hemagglutinin, responsible for receptor recognition, and fusion protein were able to overcome this transduction block. They use either the natural MV receptors, CD46 and signaling lymphocyte activation molecule (SLAM), for cell entry (MV-LV) or the vector particles were further modified to selectively enter via the CD20 molecule, which is exclusively expressed on B lymphocytes (CD20-LV). It has been shown previously that transduction by MV-LV does not induce B lymphocyte activation. However, if this is also true for CD20-LV is still unknown. Here, we generated a vector specific for another B lymphocyte marker, CD19, and compared its ability to transduce resting B lymphocytes with CD20-LV. The vector (CD19ds-LV) was able to stably transduce unstimulated B lymphocytes, albeit with a reduced efficiency of about 10% compared to CD20-LV, which transduced about 30% of the cells. Since CD20 as well as CD19 are closely linked to the B lymphocyte activation pathway, we investigated if engagement of CD20 or CD19 molecules by the vector particles induces activating stimuli in resting B lymphocytes. Although, activation of B lymphocytes often involves calcium influx, we did not detect elevated calcium levels. However, the activation marker CD71 was substantially up-regulated upon CD20-LV transduction and most importantly, B lymphocytes transduced with CD20-LV or CD19ds-LV entered the G1b phase of cell cycle, whereas untransduced or MV-LV transduced B lymphocytes remained in G0. Hence, CD20 and CD19 targeting vectors induce activating stimuli in resting B lymphocytes, which most likely renders them susceptible for lentiviral vector transduction

Mechanisms Suppressing Superheavy Element Yields in Cold Fusion Reactions

Superheavy elements are formed in fusion reactions which are hindered by fast nonequilibrium processes. To quantify these, mass-angle distributions and cross sections have been measured, at beam energies from below-barrier to 25% above, for the reactions of 48Ca,50Ti, and 54Cr with 208 Pb. Moving from 48Ca to 54Cr leads to a drastic fall in the symmetric fission yield, which is reflected in the measured mass-angle distribution by the presence of competing fast nonequilibrium deep inelastic and quasifission processes. These are responsible for reduction of the compound nucleus formation probablity PCN (as measured by the symmetric-peaked fission cross section), by a factor of 2.5 for 50Ti and 15 for 54Cr in comparison to 48 Ca. The energy dependence of PCN indicates that cold fusion reactions (involving 208Pb) are not driven by a diffusion process.The authors acknowledge the Australian Research Council for support through Discovery Grants No. DP140101337, No. DP160101254, No. DP170102318, No. FL110100098, and No. DE140100784. Financial support from the NCRIS HIA capability for operation of the Heavy Ion Accelerator Facility is acknowledged. The authors acknowledge the support of the German Academic Exchange Service (DAAD) via funds of the German Federal Ministry of Education and Research (BMBF)

Loss of Akt activity increases circulating soluble endoglin release in preeclampsia:identification of inter-dependency between Akt-1 and heme oxygenase-1

Aims - Endothelial dysfunction is a hallmark of preeclampsia. Desensitization of the phosphoinositide 3-kinase (PI3K)/Akt pathway underlies endothelial dysfunction and haeme oxygenase-1 (HO-1) is decreased in preeclampsia. To identify therapeutic targets, we sought to assess whether these two regulators act to suppress soluble endoglin (sEng), an antagonist of transforming growth factor-ß (TGF-ß) signalling, which is known to be elevated in preeclampsia. Methods and results - Vascular endothelial growth factor-A (VEGF-A), fibroblast growth factor (FGF-2), angiopoietin-1 (Ang-1), and insulin, which all activate the PI3K/Akt pathway, inhibited the release of sEng from endothelial cells. Inhibition of the PI3K/Akt pathway, by overexpression of phosphatase and tensin homolog (PTEN) or a dominant-negative isoform of Akt (Aktdn) induced sEng release from endothelial cells and prevented the inhibitory effect of VEGF-A. Conversely, overexpression of a constitutively active Akt (Aktmyr) inhibited PTEN and cytokine-induced sEng release. Systemic delivery of Aktmyr to mice significantly reduced circulating sEng, whereas Aktdn promoted sEng release. Phosphorylation of Akt was reduced in preeclamptic placenta and this correlated with the elevated level of circulating sEng. Knock-down of Akt using siRNA prevented HO-1-mediated inhibition of sEng release and reduced HO-1 expression. Furthermore, HO-1 null mice have reduced phosphorylated Akt in their organs and overexpression of Aktmyr failed to suppress the elevated levels of sEng detected in HO-1 null mice, indicating that HO-1 is required for the Akt-mediated inhibition of sEng. Conclusion - The loss of PI3K/Akt and/or HO-1 activity promotes sEng release and positive manipulation of these pathways offers a strategy to circumvent endothelial dysfunction

Experimental study of high-lying states in ²⁸Mg using the resonant elastic scattering of α particles

International audienceThe excitation function of Mg28 above the α-decay threshold has been measured for the first time using the resonant scattering of α particles with the technique of a thick target in inverse kinematics. Thirteen new states are reported between Ex=15.5 and Ex=20.5 MeV, and suggestions for spin-parity assignments are given for two of these. Calculations of the branching ratio to α decay for these states as well as comparison of the measured cross sections to calculations suggest that α+Neg.s.24 clustering is not dominant in this energy regime

Discussions and Reviews : Toward an ethology of human conflict: a review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67149/2/10.1177_002200276701100310.pd

Healthcare finance in the Kingdom of Saudi Arabia:a qualitative study of householders’ attitudes

Background: The public sector healthcare system in Saudi Arabia, essentially financed by oil revenues and ‘free at the point of delivery’, is coming under increasing strain due to escalating expenditure and an increasingly volatile oil market and is likely to be unsustainable in the medium to long term. Objectives: This study examines how satisfied the Saudi people are with their public sector healthcare services and assesses their willingness to contribute to financing the system through a national health insurance scheme. The study also examines public preferences and expectations of a future national health insurance system. Methods: A total of 36 heads of households participated in face-to-face audio-recorded semi-structured interviews. The participants were purposefully selected based on different socio-economic and socio-demographic factors from urban and rural areas to represent the geographical diversity that would presumably influence individual views, expectations, preferences and healthcare experiences. Results: The evidence showed some dissatisfaction with the provision and quality of current public sector healthcare services, including the availability of appointments, waiting times and the availability of drugs. The households indicated a willingness to contribute to a national insurance scheme, conditional upon improvements in the quality of public sector healthcare services. The results also revealed a variety of preferences and expectations regarding the proposed national health insurance scheme. Conclusions: Quality improvement is a key factor that could motivate the Saudi people to contribute to financing the healthcare system. A new authority, consisting of a partnership between the public and private sectors under government supervision, could represent an acceptable option for addressing the variation in public preferences